Neuroscience

The anatomy and physiology of olivocochlear (OC) efferents are reviewed. To help interpret these, recent advances in cochlear mechanics are also reviewed. Lateral OC (LOC) efferents innervate primary auditory-nerve (AN) fiber dendrites. The most important LOC function may be to reduce auditory neuropathy. Medial OC (MOC) efferents innervate the outer hair cells (OHCs) and act to turn down the gain of cochlear amplification. Cochlear amplification had been thought to act only through basilar membrane (BM) motion, but recent reports show that motion near the reticular lamina (RL) is amplified more than BM motion, and that RL-motion amplification extends to several octaves below the local characteristic frequency. Data on efferent effects on AN-fiber responses, otoacoustic emissions (OAEs) and human psychophysics are reviewed and reinterpreted in the light of the new cochlear-mechanical data. The possible origin of OAEs in RL motion is considered. MOC-effect measuring methods and MOC-induced changes in human responses are also reviewed, including that ipsilateral and contralateral sound can produce MOC effects with different patterns across frequency. MOC efferents help to reduce damage due to acoustic trauma. Many, but not all, reports show that subjects with stronger contralaterally-evoked MOC effects have better ability to detect signals (e.g. speech) in noise, and that MOC effects can be modulated by attention.

Based on diblock copolymers, a pair of "schizophrenic" micellar systems is designed by combining a nonionic and thermoresponsive block with a zwitterionic block, which is thermoresponsive and salt-sensitive. The nonionic block is poly(N-isopropylacrylamide) (PNIPAM) or poly(N-isopropylmethacrylamide) (PNIPMAM) and exhibits a lower critical solution temperature (LCST) behavior in aqueous solution. The zwitterionic block is a polysulfobetaine, i.e., poly(4-((3-methacrylamidopropyl)dimethylammonio)butane-1-sulfonate) (PSBP), and has an upper critical solution temperature (UCST) behavior with the clearing point decreasing with increasing salt concentration. The PSBP-b-PNIPAM and PSBP-b-PNIPMAM diblock copolymers are prepared by successive reversible addition-fragmentation chain transfer (RAFT) polymerizations. The PSBP block is chosen such that the clearing point of the homopolymer is significantly higher in pure water than the cloud point of PNIPAM or PNIPMAM. Using turbidimetry, 1 H NMR, and small-angle neutron scattering, we investigate the overall phase behavior as well as the structure and interaction between the micelles and the intermediate phase, both in salt-free D 2 O and in 0.004 M NaBr in D 2 O in a wide temperature range. We find that PSBP-b-PNIPAM at 50 g L -1 in salt-free D 2 O is turbid in the entire temperature range. It forms spherical micelles below the cloud point of PNIPAM and cylindrical micelles above. Similar behavior is observed for PSBP-b-PNIPMAM at 50 g L -1 in salt-free D 2 O with a slight and smooth increase of the light transmission below the cloud point of PNIPMAM and an abrupt decrease above. Upon addition of 0.004 M NaBr, the UCSTtype cloud point of the PSBP-block is notably decreased, and an intermediate regime is encountered below the cloud point of PNIPMAM, where the light transmission is slightly enhanced. In this regime, the polymer solution exhibits behavior typical for polyelectrolyte solutions. Thus, double thermosensitive and salt-sensitive behavior with "schizophrenic" micelle formation is found, and the width of the intermediate regime, where both blocks are hydrophilic, can be tuned by the addition of electrolyte.

Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in PTSD, and REM abnormalities after traumatic events increase the risk of developing PTSD. Therefore, it was hypothesized that abnormal REM in trauma-exposed individuals may pave the way for PTSD by interfering with the processing of extinction memory. In addition, PTSD patients display reduced vagal activity. Vagal activity contributes to the strengthening of memories, including fear extinction memory, and recent studies show that the role of vagus in memory processing extends to memory consolidation during sleep. Therefore, it is plausible that reduced vagal activity during sleep in trauma-exposed individuals may be an additional mechanism that impairs extinction memory consolidation. However, to date, the contribution of sleep vagal activity to the consolidation of extinction memory or any emotional memory has not been investigated. To test these hypotheses, we examined the association of extinction memory with REM characteristics and REM vagal activity (indexed as high-frequency heart rate variability; HF-HRV) in a large sample of trauma-exposed individuals (n=113). Consistent with our hypotheses, REM sleep characteristics (increased REM density and shortened REM latency) were associated with poorer physiological and explicit extinction memory. Furthermore, higher HF-HRV during REM was associated with better explicit extinction memory. These findings support the notion that disrupted REM may contribute to PTSD by impairing the consolidation of extinction memory and indicate the potential utility of interventions that target REM sleep characteristics and REM vagal activity in fear-related disorders.

IntroduccIón: el Boston naming test (Kaplan, Goodglass & Weintraub, 1983, 2001) es una prueba de denominación por confrontación visual que evalúa la capacidad de acceso lexical. La influencia de variables sociodemográficas es significativa en esta tarea y es importante establecer sus características en cada población. objetIvo: analizar las características psicométricas del BNT en una población de controles colombianos, las respuestas erróneas de los mismos y plantear puntos de corte según variables sociodemográficas. MaterIales y Métodos: se analiza el desempeño de 252 participantes (74 hombres, 178 mujeres, 123 < de 65, 129 > de 65 años, en tres niveles de escolaridad (60 baja, 64 media, 128 alta). Se realizó un estudio descriptivocomparativo. Se analizó la frecuencia de cada uno de los tipos de errores según los grupos de edad y escolaridad. Se realizó análisis desde la teoría clásica de los test (TCT) y se derivaron puntos de corte. resultados: se encontró que en personas mayores de 65 años y con nivel bajo de escolaridad son comunes los errores de tipo visual y de no respuesta, mientras que en personas menores de 65 años y con escolaridad alta predominan errores semánticos y visual-semánticos. Se presenta un ordenamiento de los estímulos de menor a mayor dificultad y se identifican las particularidades del desempeño de los controles colombianos estudiados. conclusIón: se resalta la importancia de la prueba en el contexto colombiano, su utilidad, y algunos criterios clínicos ofrecidos por las características de los ítems para diferenciar del envejecimiento patológico.

Dynamic modeling and simulation of signal transduction pathways is an important topic in systems biology and is obtaining growing attention from researchers with experimental or theoretical background. Here we review attempts to analyze and model specific signaling systems. We review the structure of recurrent building blocks of signaling pathways and their integration into more comprehensive models, which enables the understanding of complex cellular processes. The variety of mechanisms found and modeling techniques used are illustrated with models of different signaling pathways. Focusing on the close interplay between experimental investigation of pathways and the mathematical representations of cellular dynamics, we discuss challenges and perspectives that emerge in studies of signaling systems. <supplement> <title> <p>Problems and tools in the systems biology of the neuronal cell</p> </title> <editor>Sergio Nasi, Ivan Arisi, Antonino Cattaneo, Marta Cascante</editor> <note>Reviews</note> </supplement>

Anger is considered a unique high-arousal and approach-related negative emotion. The influence of individual differences in trait anger on the processing of visual stimuli is relevant to questions about emotional processing and remains to be explored. Using functional magnetic resonance imaging (fMRI), we explored the neural responses to standardized images, selected based on valence and arousal ratings in a group of men with high trait anger compared to those with normative to low anger scores (controls). Results show increased activation in the left-lateralized ventral fronto-parietal attention network to unpleasant images by individuals with high trait anger. There was also a group by arousal interaction in the left thalamus/pulvinar such that individuals with high trait anger had increased pulvinar activation to the high-arousal (versus low arousal) unpleasant images as compared to controls. Thus, individual differences in trait anger in men are associated with brain regions sub...

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers o...

It has been demonstrated, in a long line of research, that the low-activity genotype of the monoamine oxidase A (MAOA) gene is associated with aggression. Previous work has linked impaired response inhibition to aggression, but little is known about how this relates to the purported MAOA-aggression relationship in adolescents. Here, we examined how MAOA genotype influences neural correlates of inhibitory control in 74 healthy male adolescents using a GoStop and a Go/Nogo task while differentiating between action cancelation and action restraint. Carriers of the low-expressing MAOA alleles (MAOA-L) did not show altered brain activation in the prefrontal-subcortical inhibition network relative to carriers of the high-expressing alleles across inhibition conditions. However, they exhibited a more pronounced deactivation during response inhibition in the posterior cingulate cortex (PCC) and precuneus, areas belonging to the default mode network (DMN). Larger DMN suppression in MAOA-L ca...

While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tol...

The 2010 Julius H. Comroe, Jr., Lecture of the American Physiological Society focuses on evolving ideas in chemoreception for CO2/pH in terms of what is “sensed,” where it is sensed, and how the sensed information is used physiologically. Chemoreception is viewed as involving neurons (and glia) at many sites within the hindbrain, including, but not limited to, the retrotrapezoid nucleus, the medullary raphe, the locus ceruleus, the nucleus tractus solitarius, the lateral hypothalamus (orexin neurons), and the caudal ventrolateral medulla. Central chemoreception also has an important nonadditive interaction with afferent information arising at the carotid body. While ventilation has been viewed as the primary output variable, it appears that airway resistance, arousal, and blood pressure can also be significantly affected. Emphasis is placed on the importance of data derived from studies performed in the absence of anesthesia.

Fetal alcohol spectrum disorder (FASD) is the leading known cause of intellectual disability, and may manifest as deficits in cognitive function, including working memory. Working memory capacity and accuracy increases during adolescence when neurons in the prefrontal cortex undergo refinement. Rats exposed to low doses of ethanol prenatally show deficits in working memory during adolescence, and in cognitive flexibility in young adulthood. The cholinergic system plays a crucial role in learning and memory processes. Here we report that the combination of choline and training on a working memory task during adolescence significantly improved cognitive flexibility (performance on an attentional set shifting task) in young adulthood: 92% of all females and 81% of control males formed an attentional set, but only 36% of ethanol-exposed males did. Resting state functional magnetic resonance imaging showed that functional connectivity among brain regions was different between the sexes, and was altered by prenatal ethanol exposure and by choline + training. Connectivity, particularly between prefrontal cortex and striatum, was also different in males that formed a set compared with those that did not. Together, these findings indicate that prenatal exposure to low doses of ethanol has persistent effects on brain functional connectivity and behavior, that these effects are sex-dependent, and that an adolescent intervention could mitigate some of the effects of prenatal ethanol exposure.

Idebenone is a synthetic quinone that on reduction in cells can bypass mitochondrial Complex I defects by donating electrons to Complex III. The drug is used clinically to treat the Complex I disease Leber&#39;s hereditary optic neuropathy (LHON), but has been less successful in clinical trials for other neurodegenerative diseases. NAD(P)H:quinone oxidoreductase 1 (NQO1) appears to be the main intracellular enzyme catalyzing idebenone reduction. However, NQO1 is not universally expressed by cells of the brain. Using primary rat cortical cells pooled from both sexes, we tested the hypotheses that the level of endogenous NQO1 activity limits the ability of neurons, but not astrocytes, to use idebenone as an electron donor to support mitochondrial respiration. We then tested the prediction that NQO1 induction by pharmacological activation of the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) enables idebenone to bypass Complex I in cells with poor NQO1 expression. We ...

Males are more susceptible than females to long-term cognitive deficits following neonatal hypoxic-ischemic encephalopathy (HIE). Mitochondrial dysfunction is implicated in the pathophysiology of cerebral hypoxia-ischemia (HI), but the influence of sex on mitochondrial quality control (MQC) after HI is unknown. Therefore, we tested the hypothesis that mitophagy is sexually dimorphic and neuroprotective 20-24 h following the Rice-Vannucci model of rat neonatal HI at postnatal day 7 (PN7). Mitochondrial and lysosomal morphology and degree of colocalization were determined by immunofluorescence in the cerebral cortex. No difference in mitochondrial abundance was detected in the cortex after HI. However, net mitochondrial fission increased in both hemispheres of female brain, but was most extensive in the ipsilateral hemisphere of male brain following HI. Basal autophagy, assessed by immunoblot for the autophagosome marker LC3BI/II, was greater in males suggesting less intrinsic reserve capacity for autophagy following HI. Autophagosome formation, lysosome size, and TOM20/LAMP2 colocalization were increased in the contralateral hemisphere following HI in female, but not male brain. An accumulation of ubiquitinated mitochondrial protein was observed in male, but not female brain following HI. Moreover, neuronal cell death with NeuN/TUNEL co-staining occurred in both hemispheres of male brain, but only in the ipsilateral hemisphere of female brain after HI. In summary, mitophagy induction and neuronal cell death are sex dependent following HI. The deficit in elimination of damaged/dysfunctional mitochondria in the male brain following HI may

Hypoxia ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the developing brain, which has unique challenges from the adult. Using a model of term HI in the rat we have explored the impact of this insult on cell genesis in the hippocampus of males and females and the ability of estradiol treatment immediately after insult to restore function. Both short-term (3 days) and long-term (7 days) postinjury were assessed and revealed that only females had markedly increased cell genesis on the short-term but both sexes were increased long-term. A battery of behavioral tests revealed motor impairment in males and compromised episodic memory while both sexes were modestly impaired in spatial memory. Juvenile social play was also depressed in both sexes after HI. Estradiol therapy improved behavioral performance in both sexes but did not reverse a deficit in hippocampal volume ipsilateral to the insult. Thus the effects of estradiol do not appear to be via cell death or proliferation but rather involve other components of neural functioning.

Acute stress exposure enhances classical eyeblink conditioning in male rats, whereas exposure to the same event dramatically impairs performance in females (Wood and Shors, 1998; Wood et al., 2001). We hypothesized that stress affects learning differently in males and females because different brain regions and circuits are being activated. In the first experiment, we determined that neuronal activity within the medial prefrontal cortex (mPFC) during the stressful event is necessary to disrupt learning in females. In both males and females, the mPFC was bilaterally inactivated with GABA agonist muscimol before the stressor. Inactivation prevented only the impaired performance in females; it had no consequence for performance in males. However, in the second experiment, excitation of the mPFC alone with GABA antagonist picrotoxin was insufficient to elicit the stress effect that was prevented through the inactivation of this region in females. Therefore, we hypothesized that the mPFC...

Some, but not all, types of learning and memory can influence neurogenesis in the adult hippocampus. Trace eyeblink conditioning has been shown to enhance the survival of new neurons, whereas delay eyeblink conditioning has no such effect. The key difference between the two training procedures is that the conditioning stimuli are separated in time during trace but not delay conditioning. These findings raise the question of whether temporal discontiguity is necessary for enhancing the survival of new neurons. Here we used two approaches to test this hypothesis. First, we examined the influence of a delay conditioning task in which the duration of the conditioned stimulus (CS) was increased nearly twofold, a procedure that critically engages the hippocampus. Although the CS and unconditioned stimulus are contiguous, this very long delay conditioning procedure increased the number of new neurons that survived. Second, we examined the influence of learning the trace conditioned respons...

Trace eyeblink conditioning in which a conditioned stimulus and unconditioned stimulus are separated by a gap, is hippocampal dependent and can rescue new neurons in the adult dentate gyrus from death (e.g., . Tasks requiring more training trials for reliable expression of the conditioned response are most effective in enhancing survival of neurons . To dissociate hippocampal-dependence from acquisition rate, we facilitated hippocampal-dependent trace eyeblink conditioning in two ways: a shorter trace interval and signaling the intertrial interval with a post-US cue. Trace conditioning with a shorter trace interval (250 msec) requires an intact hippocampus, and acquisition is faster relative to rats trained with a 500 msec trace interval (e.g., . Using excitotoxic hippocampal lesions, we confirmed that eyeblink conditioning with the 250 or 500 msec trace interval is hippocampal dependent. However, training with the post-US cue was not hippocampal dependent. The majority of lesion rats in this condition reached criterion of conditioned responding. To determine whether hippocampal dependence is sufficient to rescue adult generated neurons in the dentate gyrus, rats were injected with BrdU and trained in one of the three trace eyeblink arrangements one week later. Of these training procedures, only the 500 msec trace interval enhanced survival of new cells; acquisition of this task proceeded slowly relative to the 250 msec and post-US cue conditions. These data demonstrate that rate of acquisition and not hippocampal dependence determines the impact of learning on adult neurogenesis.

Exposure to acute, inescapable stress produces a facilitation of subsequent classical eyeblink conditioning in male rats. The same stress exposure produces a profound deficit in classical eyeblink conditioning in females. Activation of N-methyl-D-aspartate receptors (NMDAr) is necessary for the effect of stress on learning in males while the contribution of NMDAr activation to the deficit in learning after stress is unknown. Here, we tested the influence of D-cycloserine (DCS), a positive modulator of the NMDAr, in stressed or unstressed male and female rats. Groups of males and females were exposed to an acute stressful event. One day later, they began training with four sessions of trace eyeblink conditioning. Each day before training, they were injected with DCS (15 mg/kg) or saline. Females treated with DCS during training responded similarly to those that were untreated. However, those that were stressed and the next day treated with the drug during training did not express the typical learning deficit, i.e. they learned to time the CR very well. Because the drug was administered well after the stressor, these data indicate that DCS reversed the negative effects of stress on learning in females. In males, the effect of DCS was subtle, resulting in higher asymptotic responding, and enhanced retention in a drug-free retention test. Thus, as shown previously, training in the presence of an NMDA receptor agonist enhances associative learning and memory retention. In addition, it can reverse learning deficits that have already been induced.

The basolateral nucleus of the amygdala (BLA) has been implicated in the modulation of learning after stress. Acute inescapable stress enhances classical eyeblink conditioning in male rats, whereas the same stressor impairs eyeblink conditioning in female rats. The experiments here directly assessed whether inactivation of the BLA during stress exposure would block both the stress-induced facilitation in males and the retardation of eyeblink conditioning in females. To this end, the BLA was temporarily inactivated by infusion of the GABA agonist muscimol before acute stressor exposure. All rats were trained in a different context 24 h later. Males infused with muscimol before the stressful event did not exhibit facilitated eyeblink conditioning, whereas those infused with the vehicle emitted more conditioned responses than unstressed males. Females infused with muscimol before stress did not express a deficit in conditioning, whereas those infused with vehicle and stressed emitted f...

After denervation of adult rat abdominal muscles, the postsynaptic apparatus of neuromuscular junctions (NMJs) retains its original architecture and clustering of acetylcholine receptors (AChRs). When descending fibers of the spinal cord are surgically diverted to this muscle by a nerve grafting procedure, supraspinal glutamatergic neurons can innervate muscle fibers and restore motor function; the newly formed NMJs switch from a cholinergic to a glutamatergic-type synapse. We show here that regenerating nerve endings contact the fibers in an area occupied by cholinergic endplates. These NMJs are morphologically indistinguishable from those in controls, but they differ in the subunit composition of AChRs. Moreover, by immunofluorescence and immunoelectron microscopy, new NMJs express glutamatergic synapse markers. The >-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 partially colocalizes with AChRs, and vesicular glutamate transporter 2 is localized in the presynaptic compartment. Immunoprecipitation analysis of membranes from reinnervated muscle showed that AMPA receptor subunits GluR1 and GluR2 coimmunoprecipitate with rapsyn, the AChR-anchoring protein at the NMJ. Taken together, these results indicate that cho-linergic endplates can be targeted by new glutamatergic projections and that the clustering of AMPA receptors occurs there.

This article aims to explore the perception of pregnant women regarding collective prenatal care facilitated by educational technology, in the light of complexity thinking. Qualitative, exploratory and descriptive study conducted between August and November 2022. The participants were 19 pregnant women from a Family Health Strategy in the central region of the State of Rio Grande do Sul. Data were collected through individual interviews following prenatal meetings and analyzed using thematic analysis. The analysis of the data revealed three thematic axes: Prenatal care: the necessary reconnection of knowledge; Collective prenatal care: collaborative (re)construction of experiences and practices; and Educational technology: tool to foster self-reflection and self-knowledge. Collective prenatal care, facilitated by educational technology, can promote better practices in the pregnancy-postpartum journey by creating collaborative and shared environments for knowledge construction and enabling autonomous and informed decision-making.

During aroused states of the brain, electroencephalographic activity is characterized by fast, irregular fluctuations of low amplitude, which are thought to reflect desynchronization of neuronal activity. This phenomenon seems at odds with the proposal that synchro- nization of cortical responses may play an important role in the processing of sensory signals. Here, activation of the mesencephalic reticular formation (MRF), an effective way to "desynchronize the electroencephalogram," was shown to facilitate oscillatory activity in the gamma frequency range and to enhance the stimulus-specific synchronization of neuronal spike responses in the visual cortex of cats. Abteilung Neurophysiologie, Max-Planck-lnstitut fur Him- forschung, Deutschordenstrasse 46,

Recent theoretical studies have suggested that oscillatory firing patterns with frequencies in the gamma band (30-70 Hz) may be instrumental for the establishment of synchrony among widely distributed neurons if synchrony is to be achieved by reciprocal connections. We have now investigated the relationship between synchrony and oscillations in cat visual cortex. Our results show that when synchronization of neuronal activity occurs over distances of &gt; 2 mm in primary visual cortex, or occurs between the two hemispheres, it is almost always associated with oscillatory firing patterns, whereas synchronization over short distances occurs also in the absence of oscillations. Furthermore, our results indicate that short-range interactions affect both the firing rate of the respective neurons and the timing of their discharges, whereas only the latter is influenced by long-range interactions. These data support the hypothesis that oscillatory activity can contribute to the establishme...

In areas 17 and 18 of the cat visual cortex the firing probability of neurons, in response to the presentation of optimally aligned light bars within their receptive field, oscillates with a peak frequency near 40 Hz. The neuronal firing pattern is tightly correlated with the phase and amplitude of an oscillatory local field potential recorded through the same electrode. The amplitude of the local field-potential oscillations are maximal in response to stimuli that match the orientation and direction preference of the local cluster of neurons. Single and multiunit recordings from the dorsal lateral geniculate nucleus of the thalamus showed no evidence of oscillations of the neuronal firing probability in the range of 20-70 Hz. The results demonstrate that local neuronal populations in the visual cortex engage in stimulus-specific synchronous oscillations resulting from an intracortical mechanism. The oscillatory responses may provide a general mechanism by which activity patterns in...

The Ca2+ increase in dendrites that is evoked by the backpropagation of somatic action potentials (APs) is involved in the activity-dependent modulation of dendritic and synaptic functions that are location dependent. In the present study, we investigated dendritic Ca2+ dynamics evoked by backpropagating APs (bAPs) in four subtypes of inhibitory interneurons classified by their spiking patterns: fast spiking (FS), late spiking (LS), burst spiking (BS), and regular-spiking nonpyramidal (RSNP) cells. Cluster analysis, single-cell RT-PCR, and immunohistochemistry confirmed the least-overlapping nature of the grouped cell populations. Somatic APs evoked dendritic Ca2+ transients in all subtypes of inhibitory interneurons with different spatial profiles along the tree: constantly linear in FS and LS cells, increasing to a plateau in BS cells and bell-shaped in RSNP cells. The increases in bAP-evoked dendritic Ca2+ transients brought about by the blocking of A-type K+ channels were simila...

The method of one-dimensional current source density (CSD) analysis was applied to field potentials recorded from 350 ~tm thick slices of the primary visual cortex of rats and cats. Field potentials were elicited by stimulation of the white matter and recorded along trajectories perpendicular to the cortical layers at spatial intervals of 25 to 50 ~m. The resulting CSD distributions resembled closely those recorded from the cat visual cortex "in vivo'. The responses with the shortest latency were distinct sinks in layers IV and VI probably reflecting monosynaptic EPSP's from specific thalamic afferents. From layer IV activity was relayed along three major routes: 1. to the supragranular layers via strong local connections to layer III and from there via both short and long range connections to layer II, 2. to targets within layer IV, and 3. to layer V. The source distributions suggest that the projections to layers III and II terminate on the proximal and distal segments, respectively, of apical dendrites of layer III pyramidal cells while the projection to layer V contacts the apical dendrites of layer VI pyramidal cells. These results indicate that all the excitatory pathways that are detectable with the CSD technique in the "in vivo" preparation remain intact in 350 ~m thick cortical slices. However, in the slice paired pulse stimulation did not lead to a depression of the response to the second stimulus while this is the case "in vivo". This might be due to reduced inhibition in the slice which has been reported by several authors.

ti' has been shown previously that surgical lesions of the antero-medial thalamus interfere with ocu!ar dominance modifications that normally result from monocular deprivation in young kittens-(Siner, 1982Y The aim of the present study was to determine whether this effect was due specifically to the destruction of the visual cortical projections of the anterior intralaminar nuclei. We report here that large excitotoxin lesions of the anterior dorsal thalamus have no effect on the cortical response to monocular deprivation. These data indicate that the intralaminar projection is not essential for ocular dominance plasticity-..

During a critical period of postnatal development the visual cortex of kittens is susceptible to experience-dependent modifications of neuronal response properties. Evidence is accumulating that these modifications are triggered by a transient neuronal calcium (Ca) influx. To further investigate this issue we measured extracellular Ca concentrations with ion-sensitive microelectrodes and compared the magnitude and the distribution of stimulus-evoked Ca fluxes in slices of the visual cortex of 4-to 5-week-old kittens and of 6-monthold adult cats. Stimulation of the white matter at 15 Hz for 8 s caused transient decreases of the extracellular Ca concentration (A Cao) in slices of both age groups and in all cortical layers. However, there were developmental changes in the laminar distribution of the A Cao: in kittens, they were maximal in layer IV whereas in adult cats they were most pronounced in the supragranular layers. The ratios between the amplitudes of ACao in layer IV and the supragranular layers were 1.65 + 0.26 in kittens and 0.43!0.2 in adult cats. These changes in laminar distribution resemble the laminar specific decay of neuronal malleability and parallel the developmental redistribution of 1,4-Dihydropyridine-sensitive Ca channels. Because of these correlations we interpret our findings as support for the hypothesis that experience-dependent modifications are triggered by Ca influx.

The mesencephalic reticular formation (MRF) of cats anesthetized with NeO was stimulated electrically, and the effects of this stimulation on activity in the striate cortex were studied. The variations of intra-and extracellularly recorded unit activity and the changes in the extracellular potassium concentration were investigated. At all levels of analysis the prevailing effect of MRF stimulation was facilitation. Half of the cells reacted with brief bursts of activity to reticular stimuli. A decrease of resting activity was rare. The cells activated by MRF stimulation had in common: (l) to show a high degree of excitatory convergence from extrinsic and intrinsic afferents, (2) to possess often corticofugal axons, and (3) to have preferentially complex receptive fields. In the large majority of cortical cells MRF stimulation facilitated responses evoked by stimulation of the optic radiation or by light stimuli. This facilitation could lead to a loss of orientation and direction selectivity. Reticular activation further led to a large increase of the extracellular potassium concentration, whereas stimulation of specific afferents led to a decrease. It is concluded that these phenomena are not merely a consequence of altered thalamic transmission, but are caused by a projection system which is organized in parallel to the specific projection and exerts a direct control over cortical excitability. The mechanism for this control appears to be a slight and rather unselective depolarization of most neurons. If disinhibitory processes are involved at all, their role is much less prominent than at the thalamic level. The functional implications of such an unselective but powerful modulation of cortical excitability are discussed in respect to corollary reticular activation as it occurs with rapid eye movements.

Accumulating evidence suggests that the development of the cat visual system is dependent on visual experience. Visual deprivation results in the loss of functional specificity in cortical neurons6,10, 22 and it is possible to cause specific and long lasting changes in the functional properties of cortical neurons 2,3,7,8,11-13,~7,21 by brief selective exposure during the critical period. In particular, it has been shown that cortical neurons become orientation-selective in the same axis as the visual stimuli presented during exposure3,8,13. If exposed to stimuli which lack orientation cues, cortical cells lose or fail to develop orientation specificity H. Cortical units in mature cats are sensitive not only to specific shapes but also selective for the speed and the direction of moving contrasts. It has recently been shown as well, that stimulus movement is a crucial parameter in the development of such normal cortical selectivity 4. With these considerations in mind, we therefore attempted to determine the extent to which dynamic RF properties such as direction selectivity and velocity tuning can be modified by selective visual exposure. Kittens which had been reared with both eyes occluded from birth were exposed, beginning at the age of 4 weeks, to vertically oriented stripes which covered the entire visual field and moved in only one direction. The kittens were placed in a restraining chair which prevented them from rotating or inclining their heads. The chair was mounted in the center of a rotating drum the walls of which were covered with a grating. The pattern had a uniform spatial frequency (0.1 c/°) and moved from left to right with an angular velocity of 15°/sec. This speed was chosen since in the adult cat it reliably activates both sustained and transient LGN cells 15. The exposure time varied from 3 to 12 h and was segmented in daily sessions of 3 h. The recordings from single units in areas 17 and 18 were performed 4-6 weeks after exposure. For surgery the kittens were anesthetized with ether and for recording the animals were curarized and anesthetized with nitrous oxide. The pupils were dilated with atropine and the corneae protected with contact lenses containing artificial pupils of 2 mm diameter. Refractive errors were measured with a Rhodenstock refractometer and corrected if necessary. The neuron samples obtained from each of the 4 kittens ranged

relaxed. An object can be also be described by an imperfectly closed boundary together with constant texture or known structure. Now, what is required for this? First, a possibility to group V1 cells without destroying their filtering properties, which is clearly provided by P&S. Second, the process must be cascadable, that is, groups of groups must be possible. This is a bit more problematic, because the number of different synchronized groups at a time is very limited. For the system proposed here, this is not a serious problem, because the processors keep their RF properties intact, so the relevant cells for a whole object may be synchronized into one group without confusion. For implementing, for example, a graph structure like the one used by it might constitute a serious limitation. If such object descriptions develop in a self-organized way based on the input image it should be relatively easy to match them with stored models of objects, although the integration of flexible matching and associative memory remains an open problem. Anyway, the target article opens a couple of interesting new routes of investigation.

The article aims to identify social impact activities in the context of information operations conducted by Ukraine during the 2022 war. An analysis of the creation and spread of information threats as a result of Russia's ongoing conflict is driven by the increasing impact of communication on global security. The content of the study highlights the impact of trends in the creation of information threats, which are the determinants of social risks. In the article, an analysis of creating information threats, including producing and reporting information in propaganda and the traditional and modern media, is of significant importance. The impact and role of mass media on awareness-raising is presented, revealing mechanisms for influencing public opinion.

Pre-trained language models (PLMs) have shown impressive performance in various language tasks. However, they are prone to spurious correlations, and often generate illusory information. In real-world applications, PLMs should justify decisions with formalized, coherent reasoning chains, but this challenge remains under-explored. Cognitive psychology theorizes that humans are capable of utilizing fast and intuitive heuristic thinking to make decisions based on past experience, then rationalizing the decisions through slower and deliberative analytic reasoning. We incorporate these interlinked dual processes in fine-tuning and in-context learning with PLMs, applying them to two language understanding tasks that require coherent physical commonsense reasoning. We show that our proposed Heuristic-Analytic Reasoning (HAR) strategies drastically improve the coherence of rationalizations for model decisions, yielding state-of-the-art results on Tiered Reasoning for Intuitive Physics (TRIP). We also find that this improved coherence is a direct result of more faithful attention to relevant language context in each step of reasoning. Our findings suggest that human-like reasoning strategies can effectively improve the coherence and reliability of PLM reasoning.

, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has posed a global challenge since December 2019. This study aimed to explore risk perceptions, knowledge, and information sources among prenatal and postnatal women at Jinja Regional Referral Hospital (JRRH) -a group particularly vulnerable to the pandemic's impact. Using a cross-sectional approach, 209 women were surveyed, employing a thematic questionnaire. Data analysis involved coding and input into Epi Info version 7, then exported to SPSS version 22.0 for analysis. Descriptive statistics summarized variables: numerical data as means and standard deviations, and categorical data as frequencies and proportions. Chi-square tests assessed associations between variables, with inferential statistics exploring relationships among study variables. Statistical Package for the Social Sciences version 26.0 conducted all analyses, with significance set at α = 0.05. Prenatal and postnatal women at JRRH perceived a lower risk of contracting or succumbing to COVID-19 compared to influenza, yet many expressed concerns about potential COVID-19 infection. Overall, participants demonstrated adequate knowledge about the disease. Their primary information sources were doctors, nurses/midwives, and television, which they regarded highly. Notably, there was no significant relationship found between perceived risk of contracting COVID-19 and knowledge levels. These findings offer insights to healthcare *adequate knowledge, participants had misconceptions regarding some World Health Organization recommendations. Addressing these misunderstandings is crucial in improving preventive practices among this vulnerable demographic.

We have recently reported that early maternal deprivation (MD) for 24 h [postnatal day (PND) 9-10] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (CP) [0.4 mg/ kg, PND 28-42] in Wistar rats induced, in adulthood, diverse sex-dependent long-term behavioral and physiological modifications. Here we show the results obtained from investigating the immunohistochemical analysis of CB1 cannabinoid receptors, glial fibrillary acidic protein (GFAP) positive (+) cells and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of the same animals. MD induced, in males, a significant increase in the number of GFAP+ cells in CA1 and CA3 areas and in the polymorphic layer of the dentate gyrus (DG), an effect that was attenuated by CP in the two latter regions. Adolescent cannabinoid exposure induced, in control non-deprived males, a significant increase in the number of GFAP+ cells in the polymorphic layer of the DG. MD induced a decrease in CB1 expression in both sexes, and this effect was reversed in males by the cannabinoid treatment. In turn, the drug "per se" induced, in males, a general decrease in CB1 immunoreactivity, and the opposite effect was observed in females. Cannabinoid exposure tended to reduce BDNF expression in CA1 and CA3 of females, whereas MD counteracted this trend and induced an increase of BDNF in females. As a whole, the present results show sex-dependent long-term effects of both MD and juvenile cannabinoid exposure as well as functional interactions between the two treatments.

Transcription disequilibria are characteristic of many neurodegenerative diseases. The activity-evoked transcription of immediate early genes (IEGs), important for neuronal plasticity, memory and behavior, is altered in CNS diseases and governed by epigenetic modulation. KDM1A, a histone 3 lysine 4 demethylase that forms part of transcription regulation complexes, has been implicated in the control of IEG transcription. Here we report the development of vafidemstat (ORY-2001), a brain penetrant inhibitor of KDM1A and MAOB. ORY-2001 efficiently inhibits brain KDM1A at doses suitable for long term treatment, and corrects memory deficit as assessed in the novel object recognition testing in the Senescence Accelerated Mouse Prone 8 (SAMP8) model for accelerated aging and Alzheimer's disease. Comparison with a selective KDM1A or MAOB inhibitor reveals that KDM1A inhibition is key for efficacy. ORY-2001 further corrects behavior alterations including aggression and social interaction deficits in SAMP8 mice and social avoidance in the rat rearing isolation model. ORY-2001 increases the responsiveness of IEGs, induces genes required for cognitive function and reduces a neuroinflammatory signature in SAMP8 mice. Multiple genes modulated by ORY-2001 are differentially expressed in Late Onset Alzheimer's Disease. Most strikingly, the amplifier of inflammation S100A9 is highly expressed in LOAD and in the hippocampus of SAMP8 mice, and down-regulated by ORY-2001. ORY-2001 is currently in multiple Phase IIa studies.

Chronic subordinate colony housing (CSC, 19 days, 12 h/12 h light/dark cycle (LDC), normal drinking water (NW)), an established model for chronic psychosocial stress in male mice, has been repeatedly shown to cause basal evening hypocorticism, spontaneous colitis and increased anxiety-related behavior. However, running this model at a novel facility under slightly different environmental conditions (14 h/10 h LDC, acidified drinking water (AW)) revealed that both, the physiology of single housed control (SHC) mice as well as the extremely robust CSC effects are strongly dependent on the prevailing environmental conditions. Notably, a 14 h/10 h LDC and AW represent standard housing conditions in many animal facilities, whereas commercial animal suppliers (e.g. Charles River, Sulzfeld, Germany) often employ a 12 h/12 h LDC and NW. In detail, our data indicate that SHC mice kept under a 14 h/10 h LDC and AW, even 4 weeks after delivery from Charles River show increased basal morning plasma corticosterone (CORT) levels. This effect was even more pronounced two weeks after arrival and could be completely prevented by employing a 12 h/12 h LDC. Importantly, using a 12 h/12 h LDC, but keeping an AW, did not bring back any of the above described CSC effects. However, the combination of a 12 h/12 h LDC and NW, instead of AW, at least brought back the well-known effects of CSC on HPA axis functionality, namely basal evening hypocorticism and a reduced adrenal in vitro ACTH sensitivity. Given that CSC exposure under these conditions still does not cause anxiety and colitis, we are currently investigating other environmental factors that might play a role.

Despite extensive research on the impact of emotional stressors on brain function using immediate-early genes (e.g., c-fos), there are still important questions that remain unanswered such as the reason for the progressive decline of c-fos expression in response to prolonged stress and the neuronal populations activated by different stressors. This study tackles these 2 questions by evaluating c-fos expression in response to 2 different emotional stressors applied sequentially, and performing a fluorescent double labeling of c-Fos protein and c-fos mRNA on stress-related brain areas. Results were complemented with the assessment of the hypothalamic-pituitary-adrenal axis activation. We showed that the progressive decline of c-fos expression could be related to 2 differing mechanisms involving either transcriptional repression or changes in stimulatory inputs. Moreover, the neuronal populations that respond to the different stressors appear to be predominantly separated in high-level processing areas (e.g., medial prefrontal cortex). However, in low-hierarchy areas (e.g., paraventricular nucleus of the hypothalamus) neuronal populations appear to respond unspecifically. The data suggest that the distinct physiological and behavioral consequences of emotional stressors, and their implication in the development of psychopathologies, are likely to be closely associated with neuronal populations specifically activated by each stressor.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Scopo del lavoro è stato: (1) monitorare il comportamento di asine, in condizioni basali e dopo somministrazione di stimoli esterni che si presentano durante le Attività Assistite con gli Animali (AAA) e le Terapie Assistite con gli Animali (TAA); (2) valutare il benessere degli stessi soggetti attraverso la determinazione delle concentrazioni di cortisolo fecale; (3) creare un protocollo operativo ripetibile, utile all'identificazione e scelta di soggetti da coinvolgere nelle attività specifiche. È stato osservato il comportamento di 10 asine divise in tre gruppi per taglia e fascia di età (A -piccola taglia, 5-9 anni; Bpiccola taglia 1,5-3 anni e C -grande taglia 4-15 anni) in condizioni basali e dopo somministrazione di stimoli esterni. Sono stati valutati: avvicinamento, con attribuzione di un punteggio crescente da 1 a 5 in base al tempo trascorso tra somministrazione e risposta (1 per tempi di avvicinamento inferiori a 10" e 5 maggiori di 60") e con valore 0 per il mancato avvicinamento; esplorazione, blocco, attacco e fuga indicando con si/no il verificarsi o meno per ciascun stimolo. I risultati sono stati espressi come frequenza percentuale. La correlazione tra il lavoro ed il benessere animale, è stata determinata attraverso la concentrazione di cortisolo fecale prima di ogni stimolo e per i successivi sette giorni mediante l'utilizzo di un kit radioimmunologico validato per il cavallo (scelto per affinità di famiglia e genere), in quanto non sono reperibili in letteratura lavori che validano l'interpretazione del kit nell'asino. L'analisi comportamentale ha evidenziato risposte significative per la scelta dei soggetti più idonei. Le differenze di concentrazione del cortisolo fecale nei soggetti a riposo rispetto a quelli sottoposti a stimolo sono risultate statisticamente significative. Obiettivo futuro è la messa a punto, dopo attenta valutazione dei soggetti, di un protocollo validato per una scelta mirata per specifiche caratteristiche e predisposizioni, garantendo agli animali uno stato di benessere che permetta ad essi di divenire co-terapeuti nell'ambito delle diverse tipologie di progetto. Tali programmi prevedono la presenza su campo del binomio animale-conduttore, affiancato da un esperto nell'ambito del benessere animale (Animal Welfare Operator-AWO) laureato in Tutela e Benessere Animale; mentre il medico veterinario clinico comportamentalista insieme a psicologi, psicoterapeuti e fisiatri si occupano rispettivamente della scelta dei soggetti da impiegare in tali attività e delle migliori strategie terapeutiche relative agli utenti. "Articolo ricevuto dal Comitato di Redazione il 18/11/2011 ed accettato per la pubblicazione dopo revisione il 13/06/2012". Le Attività Assistite con gli Animali (AAA) e le Terapie Assistite con gli Animali (TAA) rappresentano una forma di sostegno che si instaura attraverso il rapporto interpersonale mediante parole, messaggi non verbali, tono di voce ed espressione del corpo e l'interazione con l'animale da cui l'utente può trarre giovamento . Se tale giovamento ha come fine l'aiuto intenzionale si parla di terapia. L'onoterapia si inserisce nell'ambito delle TAA/AAA. Il beneficio assistenziale e terapeutico, deriva dalle situazioni d'interazione con l'animale mediante contatto corporeo, movimento, gioco e sintonia che si instaura tra asino-utente-operatore . Lentezza, prudenza, discrezione, socievo-brought to you by CORE View metadata, citation and similar papers at core.ac.uk

The issue of gender equality in employment has given rise to numerous policies in advanced industrial countries, all aimed at tackling gender discrimination regarding recruitment, salary and promotion. Yet gender inequalities in the workplace persist. The purpose of this research is to document the psychosocial process involved in the persistence of gender discrimination against working women. Drawing on the literature on the justification of discrimination, we hypothesized that the myths according to which women&#39;s work threatens children and family life mediates the relationship between sexism and opposition to a mother&#39;s career. We tested this hypothesis using the Family and Changing Gender Roles module of the International Social Survey Programme. The dataset contained data collected in 1994 and 2012 from 51632 respondents from 18 countries. Structural equation modellings confirmed the hypothesised mediation. Overall, the findings shed light on how motherhood myths justif...