Reiterated male-to-female violence disrupts hippocampal estrogen receptor ß expression, prompting anxiety-like behavior.

Intimate partner violence (IPV) is a significant public health concern whose neurological/behavioral sequelae remain to be mechanistically explained. Using a mouse model recapitulating an IPV scenario, we evaluated the female brain neuroendocrine alterations produced by a reiterated male-to-female violent interaction (RMFVI). RMFVI prompted anxiety-like behavior in female mice whose hippocampus displayed a marked neuronal loss and hampered neurogenesis, namely reduced BrdU-DCX-positive nuclei and diminished dendritic arborization in the dentate gyrus (DG): effects paralleled by a substantial downregulation of the estrogen receptor ß (ERß). After RMFVI, the DG harbored reduced brain-derived neurotrophic factor (BDNF) pools and tyrosine kinase receptor B (TrkB) phosphorylation. Accordingly, ERß knockout (KO) mice had heightened anxiety and curtailed BDNF levels at baseline while dying prematurely during the RMFVI procedure. Strikingly, injecting an ERß antagonist or agonist into the wild-type (WT) female hippocampus enhanced or reduced anxiety, respectively. Thus, reiterated male-to-female violence jeopardizes hippocampal homeostasis, perturbing the ERß/BDNF axis and ultimately instigating anxiety and chronic stress.

False memories in cuttlefish.

Episodic memory is a reconstructive process per se: during an event, the features composing it are encoded and stored separately in the brain, then reconstructed when the event's memory is retrieved. Even with source monitoring processes (e.g., did I see or did I smell it?), some mistakes can occur. These mnemonic mistakes happen especially when different events share several features, producing overlaps difficult to discriminate, leading to the creation of false memories. The common cuttlefish has the ability to remember specific events about what happened where and when, namely episodic-like memory. In order to investigate whether this memory, such as human episodic memory, is based on reconstructive processes, we elaborated a protocol promoting false memory formation. Our results suggest that cuttlefish do form visual false memories, but not olfactory false memories. These memory errors might be the first indication of the presence of reconstructive processes in the memory of cephalopods.

Opposing serial effects of stimulus and choice in speech perception scale with context variability.

In this study, we investigated serial effects on the perception of auditory vowel stimuli across three experimental setups with different degrees of context variability. Aligning with recent findings in visual perception, our results confirm the existence of two distinct processes in serial dependence: a repulsive sensory effect coupled with an attractive decisional effect. Importantly, our study extends these observations to the auditory domain, demonstrating parallel serial effects in audition. Furthermore, we uncover context variability effects, revealing a linear pattern for the repulsive perceptual effect and a quadratic pattern for the attractive decisional effect. These findings support the presence of adaptive sensory mechanisms underlying the repulsive effects, while higher-level mechanisms appear to govern the attractive decisional effect. The study provides valuable insights into the interplay of attractive and repulsive serial effects in auditory perception and contributes to our understanding of the underlying mechanisms.

Neuropeptidergic regulation of neuromuscular signaling in larval zebrafish alters swimming behavior and synaptic transmission.

Chemical synaptic transmission is modulated to accommodate different activity levels, thus enabling homeostatic scaling in pre- and postsynaptic compartments. In nematodes, cholinergic neurons use neuropeptide signaling to modulate synaptic vesicle content. To explore if this mechanism is conserved in vertebrates, we studied the involvement of neuropeptides in cholinergic transmission at the neuromuscular junction of larval zebrafish. Optogenetic stimulation by photoactivated adenylyl cyclase evoked locomotion. We generated mutants lacking the neuropeptide-processing enzyme carboxypeptidase E (cpe), and the most abundant neuropeptide precursor in motor neurons, tachykinin (tac1). Both mutants showed exaggerated locomotion after photostimulation. Recording excitatory postsynaptic currents demonstrated overall larger amplitudes in the wild type. Exaggerated locomotion in the mutants thus reflected upscaling of postsynaptic excitability. Both mutant muscles expressed more nicotinic acetylcholine receptors (nAChRs) on their surface; thus, neuropeptide signaling regulates synaptic transmitter output in zebrafish motor neurons, and muscle cells homeostatically regulate nAChR surface expression, compensating reduced presynaptic input.

High quality, high throughput, and low-cost simultaneous video recording of 60 animals in operant chambers using PiRATeMC.

BACKGROUND: The development of Raspberry Pi-based recording devices for video analyses of drug self-administration studies has been shown to be promising in terms of affordability, customizability, and capacity to extract in-depth behavioral patterns. Yet, most video recording systems are limited to a few cameras making them incompatible with large-scale studies. NEW METHOD: We expanded the PiRATeMC (Pi-based Remote Acquisition Technology for Motion Capture) recording system by increasing its scale, modifying its code, and adding equipment to accommodate large-scale video acquisition, accompanied by data on throughput capabilities, video fidelity, synchronicity of devices, and comparisons between Raspberry Pi 3B+ and 4B models. RESULTS: Using PiRATeMC default recording parameters resulted in minimal storage (∼350MB/h), high throughput (< ∼120 seconds/Pi), high video fidelity, and synchronicity within ∼0.02 seconds, affording the ability to simultaneously record 60 animals in individual self-administration chambers for various session lengths at a fraction of commercial costs. No consequential differences were found between Raspberry Pi models. COMPARISON WITH EXISTING METHOD(S): This system allows greater acquisition of video data simultaneously than other video recording systems by an order of magnitude with less storage needs and lower costs. Additionally, we report in-depth quantitative assessments of throughput, fidelity, and synchronicity, displaying real-time system capabilities. CONCLUSIONS: The system presented is able to be fully installed in a month's time by a single technician and provides a scalable, low cost, and quality-assured procedure with a high-degree of customization and synchronicity between recording devices, capable of recording a large number of subjects and timeframes with high turnover in a variety of species and settings.

Kv2 channels do not function as canonical delayed rectifiers in spinal motoneurons.

The increased muscular force output required for some behaviors is achieved via amplification of motoneuron output via cholinergic C-bouton synapses. Work in neonatal mouse motoneurons suggested that modulation of currents mediated by post-synaptically clustered KV2.1 channels is crucial to C-bouton amplification. By focusing on more mature motoneurons, we show that conditional knockout of KV2.1 channels minimally affects either excitability or response to exogenously applied muscarine. Similarly, unlike in neonatal motoneurons or cortical pyramidal neurons, pharmacological blockade of KV2 currents has minimal effect on mature motoneuron firing in vitro. Furthermore, in vivo amplification of electromyography activity and high-force task performance was unchanged following KV2.1 knockout. Finally, we show that KV2.2 is also expressed by spinal motoneurons, colocalizing with KV2.1 opposite C-boutons. We suggest that the primary function of KV2 proteins in motoneurons is non-conducting and that KV2.2 can function in this role in the absence of KV2.1.

Behavioral dysregulation in Nile tilapia (Oreochromis niloticus, GIFT) post-Streptococcus agalactia infection: Role of the microbiota-gut-brain axis.

In the aquatic farming industry, understanding the factors affecting fish behavior is crucial, particularly in response to infections that compromise welfare and productivity. Swimming performance is a key life history trait critical to their ecology. This study explores the swimming behavior imbalance in Nile tilapia (Oreochromis niloticus, GIFT) post-infection with Streptococcus agalactiae (GBS), a common pathogen responsible for significant losses in aquaculture. We focused on how the microbiota-gut-brain axis influences the behavioral response of tilapia to GBS infection. Behavioral changes were quantified by measuring collision times and swimming speeds, which decreased significantly following infection. This behavioral downturn is mediated by alterations in the microbiota-gut-brain axis, evidenced by increased levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in the brain and intestinal tissues. The study utilized pharmacological agents, the 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635), to investigate their efficacy in mitigating these behavioral and biochemical changes. Both agents partially restored normal behavior by adjusting neurotransmitter concentrations disrupted by GBS infection. Additionally, a notable increase in the relative abundance of Streptococcus within the gut microbiota of infected fish highlights the potential role of specific bacterial populations in influencing host behavior. This research provides novel insights into the complex interactions between pathogen-induced gut microbiota changes and Nile tilapia's behavioral outcomes, highlighting potential avenues for improving fish health management through microbiota-targeted interventions.

Distinct role of central predictive mechanisms in tactile suppression.

Tactile sensitivity on a limb is reduced during movement. This tactile suppression results presumably from central predictive mechanisms that downregulate sensations caused during voluntary action. Suppression also occurs during passive movements, indicating a role for peripheral mechanisms, questioning the predictive nature of suppression. Yet, predictions existing beyond the motor domain (non-motor predictions) can also modulate tactile suppression. This study aimed to disentangle central motor predictive and peripheral feedback mechanisms while accounting for non-motor predictions. Participants detected tactile stimuli on their limb shortly before it moved in an active or passive manner. Passive movements were either fully (100%) or partially (50%) predictable. We found tactile suppression during both active and passive movements irrespective of whether the passive movements were predictable. Importantly, tactile suppression was stronger in active than passive movements highlighting the specific role of central predictive mechanisms.

A shared structure for emotion experiences from narratives, videos, and everyday life.

Our knowledge of the diversity and psychological organization of emotion experiences is based primarily on studies that used a single type of stimulus with an often limited set of rating scales and analyses. Here we take a comprehensive data-driven approach. We surveyed 1,000+ participants on a diverse set of ratings of emotion experiences to a validated set of ca. 150 text narratives, a validated set of ca. 1,000 videos, and over 10,000 personal experiences sampled longitudinally in everyday life, permitting a unique comparison. All three types of emotion experiences were characterized by similar dimensional spaces that included valence and arousal, as well as dimensions related to generalizability. Emotion experiences were distributed along continuous gradients, with no clear clusters even for the so-called basic emotions. Individual differences in personality traits were associated with differences in everyday emotion experiences but not with emotions evoked by narratives or videos.

Dietary fat content and absorption shape standard diet devaluation through hunger circuits.

OBJECTIVE: Exposure to 60% high fat diet (HFD) leads to a robust consummatory preference over well-balanced chow standard diet (SD) when mice are presented with a choice. This passive HFD-induced SD devaluation following HFD challenge and withdrawal is highlighted by the significant reduction in SD food intake even in states of caloric deprivation. The elements of HFD that lead to this SD depreciation remains unclear. Possibly important factors include the amount and type of fat contained in a diet as well as past eating experiences dependent on sensory properties including taste and post ingestive feedback. We aimed to explore the role of these components to HFD-induced SD devaluation. METHODS: Wildtype mice were longitudinally presented discrete HFDs in conjunction with SD and feeding and metabolic parameters were analyzed. A separate cohort of animals were assessed for acute HFD preference in 3 conditions: 1) ad libitum fed (sated), 2) overnight fasted (physiologically hungry), and 3) ad libitum fed (artificially hungry), elicited through chemogenetic Agouti-related peptide (AgRP) neuron activation. Population dynamics of AgRP neurons were recorded to distinct inaccessible and accessible diets both before and after consummatory experience. Transient receptor potential channel type M5 (TRPM5) knockout mice were used to investigate the role of fat taste perception and preference to HFD-induced SD devaluation. The clinically approved lipase inhibitor orlistat was used to test the contribution of fat absorption to HFD-induced SD devaluation. RESULTS: HFD-induced SD devaluation is dependent on fat content, composition, and preference. This effect scaled both in strength and latency with higher percentages of animal fat. 60% HFD was preferred and almost exclusively consumed in preference to other diets across hours and days, but this was not as evident upon initial introduction over seconds and minutes, suggesting ingestive experience is critical. Optical fiber photometry recordings of AgRP activity supported this notion as neuronal suppression by the different diets was contingent on prior intake. While taste transduced via TRPM5 influenced HFD-evoked weight gain, it failed to impact either HFD preference or HFD-induced SD devaluation. Perturbation of post ingestive feedback through orlistat-mediated diminishment of fat absorption prevented HFD-evoked weight gain and abolished HFD-induced SD devaluation. CONCLUSIONS: Post ingestive feedback via fat digestion is vital for expression of HFD-induced SD devaluation.

Projection neurons from medial entorhinal cortex to basolateral amygdala are critical for the retrieval of morphine withdrawal memory.

The medial entorhinal cortex (MEC) is crucial for contextual memory, yet its role in context-induced retrieval of morphine withdrawal memory remains unclear. This study investigated the role of the MEC and its projection neurons from MEC layer 5 to the basolateral amygdala (BLA) (MEC-BLA neurons) in context-induced retrieval of morphine withdrawal memory. Results show that context activates the MEC in morphine withdrawal mice, and the inactivation of the MEC inhibits context-induced retrieval of morphine withdrawal memory. At neural circuits, context activates MEC-BLA neurons in morphine withdrawal mice, and the inactivation of MEC-BLA neurons inhibits context-induced retrieval of morphine withdrawal memory. But MEC-BLA neurons are not activated by conditioning of context and morphine withdrawal, and the inhibition of MEC-BLA neurons do not influence the coupling of context and morphine withdrawal memory. These results suggest that MEC-BLA neurons are critical for the retrieval, but not for the formation, of morphine withdrawal memory.

Cocaine disrupts action flexibility via glucocorticoid receptors.

Many addictive drugs increase stress hormone levels. They also alter the propensity of organisms to prospectively select actions based on long-term consequences. We hypothesized that cocaine causes inflexible action by increasing circulating stress hormone levels, activating the glucocorticoid receptor (GR). We trained mice to generate two nose pokes for food and then required them to update action-consequence associations when one response was no longer reinforced. Cocaine delivered in adolescence or adulthood impaired the capacity of mice to update action strategies, and inhibiting CORT synthesis rescued action flexibility. Next, we reduced Nr3c1, encoding GR, in the orbitofrontal cortex (OFC), a region of the brain responsible for interlacing new information into established routines. Nr3c1 silencing preserved action flexibility and dendritic spine abundance on excitatory neurons, despite cocaine. Spines are often considered substrates for learning and memory, leading to the discovery that cocaine degrades the representation of new action memories, obstructing action flexibility.

Exposure to elevated glucocorticoid during development primes altered transcriptional responses to acute stress in adulthood.

Early life stress (ELS) is a major risk factor for developing psychiatric disorders, with glucocorticoids (GCs) implicated in mediating its effects in shaping adult phenotypes. In this process, exposure to high levels of developmental GC (hdGC) is thought to induce molecular changes that prime differential adult responses. However, identities of molecules targeted by hdGC exposure are not completely known. Here, we describe lifelong molecular consequences of hdGC exposure using a newly developed zebrafish double-hit stress model, which shows altered behaviors and stress hypersensitivity in adulthood. We identify a set of primed genes displaying altered expression only upon acute stress in hdGC-exposed adult fish brains. Interestingly, this gene set is enriched in risk factors for psychiatric disorders in humans. Lastly, we identify altered epigenetic regulatory elements following hdGC exposure. Thus, our study provides comprehensive datasets delineating potential molecular targets mediating the impact of hdGC exposure on adult responses.

Hyperactive mTORC1 disrupts habenula function and light preference in zebrafish model of Tuberous sclerosis complex.

Mechanistic target of rapamycin complex 1 (mTORC1) is an integration hub for extracellular and intracellular signals necessary for brain development. Hyperactive mTORC1 is found in autism spectrum disorder (ASD) characterized by atypical reactivity to sensory stimuli, among other symptoms. In Tuberous sclerosis complex (TSC) inactivating mutations in the TSC1 or TSC2 genes result in hyperactivation of the mTORC1 pathway and ASD. Here, we show that lack of light preference of the TSC zebrafish model, tsc2 vu242/vu242 is caused by aberrant processing of light stimuli in the left dorsal habenula and tsc2 vu242/vu242 fish have impaired function of the left dorsal habenula, in which neurons exhibited higher activity and lacked habituation to the light stimuli. These characteristics were rescued by rapamycin. We thus discovered that hyperactive mTorC1 caused aberrant habenula function resulting in lack of light preference. Our results suggest that mTORC1 hyperactivity contributes to atypical reactivity to sensory stimuli in ASD.

Ventral zona incerta parvalbumin neurons modulate sensory-induced and stress-induced self-grooming via input-dependent mechanisms in mice.

Self-grooming is an innate stereotyped behavior influenced by sense and emotion. It is considered an important characteristic in various disease models. However, the neural circuit mechanism underlying sensory-induced and emotion-driven self-grooming remains unclear. We found that the ventral zona incerta (Ziv) was activated during spontaneous self-grooming (SG), corn oil-induced sensory self-grooming (OG), and tail suspension-induced stress self-grooming (TG). Optogenetic excitation of Ziv parvalbumin (PV) neurons increased the duration of SG. Conversely, optogenetic inhibition of ZivPV neurons significantly reduced self-grooming in all three models. Furthermore, glutamatergic inputs from the primary sensory cortex activated the Ziv and contributed to OG. Activation of GABAergic inputs from the central amygdala to the Ziv increased SG, OG, and TG, potentially through local negative regulation of the Ziv. These findings suggest that the Ziv may play a crucial role in processing sensory and emotional information related to self-grooming, making it a potential target for regulating stereotyped behavior.

Neural-circuit basis of song preference learning in fruit flies.

As observed in human language learning and song learning in birds, the fruit fly Drosophila melanogaster changes its auditory behaviors according to prior sound experiences. This phenomenon, known as song preference learning in flies, requires GABAergic input to pC1 neurons in the brain, with these neurons playing a key role in mating behavior. The neural circuit basis of this GABAergic input, however, is not known. Here, we find that GABAergic neurons expressing the sex-determination gene doublesex are necessary for song preference learning. In the brain, only four doublesex-expressing GABAergic neurons exist per hemibrain, identified as pCd-2 neurons. pCd-2 neurons directly, and in many cases mutually, connect with pC1 neurons, suggesting the existence of reciprocal circuits between them. Moreover, GABAergic and dopaminergic inputs to doublesex-expressing GABAergic neurons are necessary for song preference learning. Together, this study provides a neural circuit model that underlies experience-dependent auditory plasticity at a single-cell resolution.

Fine-grained knowledge about manipulable objects is well-predicted by contrastive language image pre-training.

Object recognition is an important ability that relies on distinguishing between similar objects (e.g., deciding which utensil(s) to use at different stages of meal preparation). Recent work describes the fine-grained organization of knowledge about manipulable objects via the study of the constituent dimensions that are most relevant to human behavior, for example, vision, manipulation, and function-based properties. A logical extension of this work concerns whether or not these dimensions are uniquely human, or can be approximated by deep learning. Here, we show that behavioral dimensions are generally well-predicted by CLIP-ViT - a multimodal network trained on a large and diverse set of image-text pairs. Moreover, this model outperforms comparison networks pre-trained on smaller, image-only datasets. These results demonstrate the impressive capacity of CLIP-ViT to approximate fine-grained object knowledge. We discuss the possible sources of this benefit relative to other models (e.g., multimodal vs. image-only pre-training, dataset size, architecture).

Choice-dependent delta-band neural trajectory during semantic category decision making in the human brain.

Recent human brain imaging studies have identified widely distributed cortical areas that represent information about the meaning of language. Yet, the dynamic nature of widespread neural activity as a correlate of the semantic information processing remains poorly explored. Our state space analysis of electroencephalograms (EEGs) recorded during semantic match-to-category task show that depending on the semantic category and decision path chosen by participants, whole-brain delta-band dynamics follow distinct trajectories that are correlated with participants' response time on a trial-by-trial basis. Especially, the proximity of the neural trajectory to category decision-specific region in the state space was predictive of participants' decision-making reaction times. We also found that posterolateral regions primarily encoded word categories while postero-central regions encoded category decisions. Our results demonstrate the role of neural dynamics embedded in the evolving multivariate delta-band activity patterns in processing the semantic relatedness of words and the semantic category-based decision-making.

Acute exposure to caffeine improves foraging in an invasive ant.

Argentine ants, Linepithema humile, are a particularly concerning invasive species. Control efforts often fall short likely due to a lack of sustained bait consumption. Using neuroactives, such as caffeine, to improve ant learning and navigation could increase recruitment and consumption of toxic baits. Here, we exposed L. humile to a range of caffeine concentrations and a complex ecologically relevant task: an open landscape foraging experiment. Without caffeine, we found no effect of consecutive foraging visits on the time the ants take to reach a reward, suggesting a failure to learn the reward's location. However, under low to intermediate caffeine concentrations ants were 38% faster with each consecutive visit, implying that caffeine boosts learning. Interestingly, such improvements were lost at high doses. In contrast, caffeine had no impact on the ants' homing behavior. Adding moderate levels of caffeine to baits could improve ant's ability to learn its location, improving bait efficacy.