An anterior hypothalamic circuit gates stress vulnerability.

Prior adversity increases susceptibility to subsequent stressful events, but the causal underlying changes in brain circuitry are poorly understood. We harnessed unbiased whole-brain activity mapping to identify circuits that are functionally remodeled by prior adversity. This revealed that the anterior hypothalamic nucleus (AHN) displays heightened stress reactivity in previously stressed mice.

Dissociable contributions of the amygdala and ventral hippocampus to stress-induced changes in defensive behavior.

Stress can have profound consequences on mental health. While much is known about the neural circuits supporting associative memories of stressful events, our understanding of the circuits underlying the non-associative impacts of stress, such as heightened stress sensitivity and anxiety-related behavior, is limited. Here, we demonstrate that the ventral hippocampus (vHC) and basolateral amygdala (BLA) support distinct non-associative behavioral changes following stress.

Simultaneous dual-color calcium imaging in freely-behaving mice.

Unlabelled: Miniaturized fluorescence microscopes (miniscopes) enable imaging of calcium events from a large population of neurons in freely behaving animals. Traditionally, miniscopes have only been able to record from a single fluorescence wavelength. Here, we present a new open-source dual-channel Miniscope that simultaneously records two wavelengths in freely behaving animals.

Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy.

Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous electrophysiology in hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits.

Aversive experience drives offline ensemble reactivation to link memories across days.

Memories are encoded in neural ensembles during learning and stabilized by post-learning reactivation. Integrating recent experiences into existing memories ensures that memories contain the most recently available information, but how the brain accomplishes this critical process remains unknown. Here we show that in mice, a strong aversive experience drives the offline ensemble reactivation of not only the recent aversive memory but also a neutral memory formed two days prior, linking the fear from the recent aversive memory to the previous neutral memory.

Dissociable contributions of the amygdala and ventral hippocampus to stress-induced changes in defensive behavior.

Background: Severe stress can produce multiple persistent changes in defensive behavior relevant to psychiatric illness. While much is known about the circuits supporting stress-induced associative fear, how stress-induced circuit plasticity supports non-associative changes in defensive behavior remains unclear.

Methods: Mice were exposed to an acute severe stressor, and subsequently, both associative and non-associative defensive behavioral responses were assessed.

Minian, an open-source miniscope analysis pipeline.

Miniature microscopes have gained considerable traction for in vivo calcium imaging in freely behaving animals. However, extracting calcium signals from raw videos is a computationally complex problem and remains a bottleneck for many researchers utilizing single-photon in vivo calcium imaging. Despite the existence of many powerful analysis packages designed to detect and extract calcium dynamics, most have either key parameters that are hard-coded or insufficient step-by-step guidance and validations to help the users choose the best parameters.

ezTrack-A Step-by-Step Guide to Behavior Tracking.

Tracking animal behavior by video is one of the most common tasks in neuroscience. Previously, we have validated ezTrack, a free, flexible, and easy-to-use software for the analysis of animal behavior. ezTrack's Location Tracking Module can be used for the positional analysis of an individual animal and is applicable to a wide range of behavioral tasks.

The Medial Orbitofrontal Cortex-Basolateral Amygdala Circuit Regulates the Influence of Reward Cues on Adaptive Behavior and Choice.

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions.

A Basomedial Amygdala to Intercalated Cells Microcircuit Expressing PACAP and Its Receptor PAC1 Regulates Contextual Fear.

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice.

Breakdown of spatial coding and interneuron synchronization in epileptic mice.

Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation.

ezTrack: An open-source video analysis pipeline for the investigation of animal behavior.

Tracking animal behavior by video is one of the most common tasks in the life sciences. Although commercial software exists for executing this task, they often present enormous cost to the researcher and can entail purchasing hardware that is expensive and lacks adaptability. Additionally, the underlying code is often proprietary.

Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma.

Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning.

Across sex and age: Learning and memory and patterns of avian hippocampal gene expression.

Age-related decrements in cognitive ability have been proposed to stem from deteriorating function of the hippocampus. Many birds are long lived, especially for their relatively small body mass and elevated metabolism, making them a unique model of resilience to aging. Nevertheless, little is known about avian age-related changes in cognition and hippocampal physiology.

A return to the psychiatric dark ages with a two-system framework for fear.

The past several decades has seen considerable progress in our understanding of the neurobiology of fear and anxiety. These advancements were spurred on by envisioning fear as emerging from the coordinated activation of brain and behavioral systems that evolved for the purpose of defense from environmental dangers. Recently, Joseph LeDoux, a previous proponent of this view, published a series of papers in which he challenges the value of this approach.

The ventromedial prefrontal cortex in a model of traumatic stress: fear inhibition or contextual processing?

The ventromedial prefrontal cortex (vmPFC) has consistently appeared altered in post-traumatic stress disorder (PTSD). Although the vmPFC is thought to support the extinction of learned fear responses, several findings support a broader role for this structure in the regulation of fear. To further characterize the relationship between vmPFC dysfunction and responses to traumatic stress, we examined the effects of pretraining vmPFC lesions on trauma reactivity and enhanced fear learning in a rodent model of PTSD.

Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations.

To make an appropriate decision, one must anticipate potential future rewarding events, even when they are not readily observable. These expectations are generated by using observable information (e.g.

Compromised NMDA/Glutamate Receptor Expression in Dopaminergic Neurons Impairs Instrumental Learning, But Not Pavlovian Goal Tracking or Sign Tracking.

Two theories regarding the role for dopamine neurons in learning include the concepts that their activity serves as a (1) mechanism that confers incentive salience onto rewards and associated cues and/or (2) contingency teaching signal reflecting reward prediction error. While both theories are provocative, the causal role for dopamine cell activity in either mechanism remains controversial. In this study mice that either fully or partially lacked NMDARs in dopamine neurons exclusively, as well as appropriate controls, were evaluated for reward-related learning; this experimental design allowed for a test of the premise that NMDA/glutamate receptor (NMDAR)-mediated mechanisms in dopamine neurons, including NMDA-dependent regulation of phasic discharge activity of these cells, modulate either the instrumental learning processes or the likelihood of pavlovian cues to become highly motivating incentive stimuli that directly attract behavior.

Dissecting impulsivity and its relationships to drug addictions.

Addictions are often characterized as forms of impulsive behavior. That said, it is often noted that impulsivity is a multidimensional construct, spanning several psychological domains. This review describes the relationship between varieties of impulsivity and addiction-related behaviors, the nature of the causal relationship between the two, and the underlying neurobiological mechanisms that promote impulsive behaviors.

Reward, interrupted: Inhibitory control and its relevance to addictions.

There are broad individual differences in the ability to voluntarily and effortfully suppress motivated, reward-seeking behaviors, and this review presents the hypothesis that these individual differences are relevant to addictive disorders. On one hand, cumulative experience with drug abuse appears to alter the molecular, cellular and circuit mechanisms that mediate inhibitory abilities, leading to increasingly uncontrolled patterns of drug-seeking and -taking. On the other, native inter-individual differences in inhibitory control are apparently a risk factor for aspects of drug-reinforced responding and substance use disorders.