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Monmita Bhar, Tanumoy Nandi, Hari Narayanan +2·Apr 3, 2026
Memory formation is necessary for the survival of animals across phyla. Here, we elucidate the mechanism underlying the formation of long-term associative memory (LTAM) formed by treating Caenorhabditis elegans with a volatile chemoattractant and heat. Previous work has shown that training animals with a paradigm involving heat and isoamyl alcohol (IAA) simultaneously, causes C. elegans to lose their attraction to IAA. In this study, we elaborate on the mechanism behind this LTAM formation and suggest that during training with heat and IAA, C. elegans release extracellular vesicles (EVs) from the IL2 neurons that upon being taken up by the same trained animals or their untrained counterparts causes the organism to lose attraction to IAA. Our data suggests that the vesicles are highly specific to the training paradigms used and differ with differing cues. Finally, we show that 2,4-Xylidine is released from trained worms and upon addition to plates allows naïve animals to behave like trained animals for upto 20 hours.
Rachel Chudoba, Joanna Dabrowska·Aug 9, 2025
The prevalence of post-traumatic stress disorder (PTSD) and anxiety disorders is higher in women than men. The severity of hallmark symptoms including hypervigilance and fear reactivity to unpredictable threats varies with sex and reproductive cycle, but the underlying mechanisms remain unclear. Here, we investigated corticotropin-releasing factor (CRF) neurons in the dorsolateral bed nucleus of the stria terminalis (BNSTDL) as a potential nexus for the influence of biological sex and reproductive cycle on fear- and anxiety-related behaviors. 125 male and 156 cycle-monitored female CRF-Cre rats were used. BNSTDL-CRF neuron excitability and synaptic activity was recorded with slice electrophysiology. Chemogenetic manipulations of BNSTDL-CRF neurons were performed before elevated-plus maze, predator odor exposure, shock-induced startle sensitization, and anxiety-potentiated startle (APS) following unpredictable fear conditioning. BNSTDL-CRF neurons in females exhibit higher excitability (cycle-independent) and lower sensitivity to excitatory synaptic inputs (proestrus and diestrus) compared to males. BNSTDL-CRF neuron inhibition reduces open-arm time in estrous females but not males. In the APS, BNSTDL-CRF neuron inhibition attenuates short-term startle potentiation in males, whereas it causes persistent APS in diestrus females. Notably, chemogenetic activation of BNSTDL-CRF neuron reduces APS in diestrus females. Unpredictable fear conditioning elicits sex- and estrous phase-specific APS, differentially regulated by BNSTDL-CRF neurons. Persistent APS in females align with hormonal phases marked by low levels of reproductive hormones, mirroring human PTSD findings. Widely used in human studies, APS may bridge animal and human research, supporting biomarker development and more effective pharmacotherapies.
Sophie V Griswold, Stephen D Van Hooser·Jul 26, 2025
Development of the mammalian visual system is thought to proceed in two stages. In the first stage, before birth in primates and before eye opening in altricial mammals, spontaneous activity generated by the retina and cortex shapes visual brain circuits in an activity- dependent but experience-independent manner. In the second stage, visual activity generated by sensory experience refines receptive fields. Here we investigated the consequences of altering this sequence of events by prematurely opening one or both eyes of ferrets and examining visual receptive fields in monocular cortex after the closure of the critical period for ocular dominance plasticity. We observed that many cells in animals with prematurely-opened eyes exhibited low-pass temporal frequency tuning and increased temporal frequency bandwidths, and these cells showed slightly increased orientation and direction selectivity index values. Spontaneous activity was greatly elevated in both hemispheres following the premature opening of one or both eyes, suggesting a global change in circuit excitability that was not restricted to cells that viewed the world through the prematurely opened eye. No major changes were noted in spatial frequency tuning. These results suggest that premature visual experience alters circuit excitability and visual receptive fields, in particular with respect to temporal processing. We speculate that closed lids in altricial mammals serve to prevent visual experience until circuits are initially established and are ready to be refined by visual experience.
Jessica A Haley, Tianyi Chen, Mikio Aoi +1·Aug 1, 2025
Decision-making is a ubiquitous component of animal behavior that is often studied in the context of foraging. Foragers make a series of decisions while locating food (food search), choosing between food types (diet or patch choice), and allocating time spent within patches of food (patch-leaving). Here, we introduce a framework for investigating foraging decisions using detailed analysis of individual behavior and quantitative modeling in the nematode Caenorhabditis elegans. We demonstrate that C. elegans make accept-reject patch choice decisions upon encounter with food. Specifically, we show that when foraging amongst small, dispersed, and dilute patches of bacteria, C. elegans initially reject several bacterial patches, opting to prioritize exploration of the environment, before switching to a more exploitatory foraging strategy during subsequent encounters. Observed across a range of bacterial patch densities, sizes, and distributions, we use a quantitative model to show that this decision to explore or exploit is guided by available sensory information, internal satiety signals, and learned environmental statistics related to the bacterial density of recently encountered and exploited patches. We behaviorally validated model predictions on animals that had been food-deprived, animals foraging in environments with multiple patch densities, and null mutants with defective sensory modalities. Broadly, we present a framework to study ecologically relevant foraging decisions that could guide future investigations into the cellular and molecular mechanisms underlying decision-making.
Walter Francesconi, Valentina Olivera-Pasilio, Fulvia Berton +6·Jun 17, 2025
Interoceptive signals dynamically interact with the environment to shape appropriate defensive behaviors. Hypothalamic hormones arginine-vasopressin (AVP) and oxytocin (OT) regulate physiological states, including water and electrolyte balance, circadian rhythmicity, and defensive behaviors. Both AVP and OT neurons project to the bed nucleus of stria terminalis (BNST), which expresses oxytocin receptors (OTR) and vasopressin receptors, and governs fear responses. However, understanding the integrated role of AVP and OT is complicated by their cross-reactivity and their mutual receptor promiscuity. Here, we provide evidence that the effects of neurohypophysial hormones on BNST excitability are driven by cell type-specific receptor selectivity and input specificity. We show that OTR-expressing BNST neurons, excited by hypothalamic AVP and OT inputs via OTR, play a major role in regulating BNST excitability, overcoming threat avoidance, and reducing threat-elicited anxious arousal. Therefore, OTR-BNST neurons are perfectly suited to drive the dynamic interactions balancing external threat risk and physiological needs.
Kristen Reikersdorfer, Andrea Stacy, David Bressler +3·Jul 7, 2024
Multichannel electrode arrays offer insight into the working brain and serve to elucidate neural processes at the single-cell and circuit levels. Development of these tools is crucial for understanding complex behaviors and cognition and for advancing clinical applications. However it remains a challenge to densely record from cell populations stably and continuously over long time periods. Many popular electrodes such as tetrodes and silicon arrays feature large cross-diameters that produce damage upon insertion and elicit chronic reactive tissue responses associated with neuronal death hindering the recording of stable continuous neural activity. In addition most wire bundles exhibit broad spacing between channels precluding simultaneous recording from a large number of cells clustered in a small area. The carbon fiber microelectrode arrays described in this protocol offer an accessible solution to these concerns. The study provides a detailed method for fabricating carbon fiber microelectrode arrays that can be used for both acute and chronic recordings in vivo. The physical properties of these electrodes make them ideal for stable and continuous long-term recordings at high cell densities enabling the researcher to make robust unambiguous recordings from single units across months.
Stephen D. Van Hooser, Arani Roy, Heather J. Rhodes +2·Apr 8, 2024
Tree shrew primary visual cortex (V1) exhibits a pronounced laminar segregation of inputs from different classes of relay neurons in the lateral geniculate nucleus (LGN). We examined how several receptive field (RF) properties were transformed from LGN to V1 layer 4 to V1 layer 2/3. The progression of RF properties across these stages differed markedly from that found in the cat. V1 layer 4 cells are largely similar to the the LGN cells that provide their input, being dominated by a single sign (ON or OFF) and being strongly modulated by sinusoidal gratings. Some layer 4 neurons, notably those near the edges of layer 4, exhibited increased orientation selectivity, and most layer 4 neurons exhibited a preference for lower temporal frequencies. Neurons in cortical layer 2/3 differ significantly from those in the LGN; most exhibited strong orientation tuning and both ON and OFF responses. The strength of orientation selectivity exhibited a notable sublaminar organization, with the strongest orientation tuned neurons in the most superficial parts of layer 2/3. Modulation indexes provide evidence for simple and complex cells in both layer 4 and layer 2/3. However, neurons with high modulation indexes were heterogenous in the spatial organization of ON and OFF responses, with many of them exhibiting unbalanced ON and OFF responses rather than well-segregated ON and OFF subunits. When compared to the laminar organization of V1 in other mammals, these data show that the process of natural selection can result in significantly altered structure/function relationships in homologous cortical circuits.
Narendra Mukherjee, Donald Katz, Joseph Wachutka·Nov 4, 2023
Sensation and action are necessarily coupled during stimulus perception – while tasting, for instance, perception happens while an animal decides to expel or swallow the substance in the mouth (the former via a behavior known as ‘gaping’). Taste responses in the rodent gustatory cortex (GC) span this sensorimotor divide, progressing through firing-rate epochs that culminate in the emergence of action-related firing. Population analyses reveal this emergence to be a sudden, coherent and variably-timed ensemble transition that reliably precedes gaping onset by 0.2–0.3s. Here, we tested whether this transition drives gaping, by delivering 0.5s GC perturbations in tasting trials. Perturbations significantly delayed gaping, but only when they preceded the action-related transition - thus, the same perturbation impacted behavior or not, depending on the transition latency in that particular trial. Our results suggest a distributed attractor network model of taste processing, and a dynamical role for cortex in driving motor behavior.