Male and female impairments in odor span are observed in a rat model of PTSD.

Posttraumatic stress disorder (PTSD) is associated with neural and behavioral alterations in response to trauma exposure, including working memory impairments. Rodent models of PTSD have not fully investigated chronic or reactive working memory deficits, despite clinical relevance. The present study uses footshock to induce a posttraumatic stress state in male and female rats and evaluates the effect of footshock and trauma-paired odor cues on working memory performance in the odor span task. Results demonstrate the emergence of chronic deficits in working memory among animals exposed to footshock by 3 wk after traumatic stress. The presentation of a trauma-paired odor cue was associated with further decrement in working memory performance for male animals. Furthermore, anxiety-like behaviors associated with the PTSD-like phenotype could predict the degree of working memory impairment in response to the trauma-paired odor cue. This study enhances validation of an existing rodent model of PTSD through replication of the clinical observations of working memory deficits associated with PTSD and provides novel insight into effects in female rodents. This will facilitate work to probe underlying mechanistic dysregulation of working memory following footshock trauma exposure and future development of novel treatment strategies.

Recurrent activity within microcircuits of macaque dorsolateral prefrontal cortex tracks cognitive flexibility.

Human and non-human primate data clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions 1,2 . It is thought that intracortical synaptic architectures within dlPFC are the integral neurobiological substrate that gives rise to these processes, including working memory, inferential reasoning, and decision-making 3-7 . In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the 'canonical' cortical microcircuit 3,8 . Each cortical microcircuit receives sensory and cognitive information from a variety of sources which are represented by sustained activity within the microcircuit, referred to as persistent or recurrent activity 4,9 . Via recurrent connections within the microcircuit, activity can propagate for a variable length of time, thereby allowing temporary storage and computations to occur locally before ultimately passing a transformed representation to a downstream output 4,5,10 . Competing theories regarding how microcircuit activity is coordinated have proven difficult to reconcile in vivo where intercortical and intracortical computations cannot be fully dissociated 5,9,11,12 . Here, we interrogated the intrinsic features of isolated microcircuit networks using high-density calcium imaging of macaque dlPFC ex vivo . We found that spontaneous activity is intrinsically maintained by microcircuit architecture, persisting at a high rate in the absence of extrinsic connections. Further, using perisulcal stimulation to evoke persistent activity in deep layers, we found that activity propagates through stochastically assembled intracortical networks, creating predictable population-level events from largely non-overlapping ensembles. Microcircuit excitability covaried with individual cognitive performance, thus anchoring heuristic models of abstract cortical functions within quantifiable constraints imposed by the underlying synaptic architecture.

ß-endorphin regulates alcohol consumption induced by exercise restriction in female mice.

Animal models have long been used to study the mechanisms underlying the complex association between alcohol and stress. Female mice prevented from running on a home-cage activity wheel increase voluntary ethanol consumption. ß-endorphin is an endogenous opioid involved in negatively regulating the stress response and has also been implicated in the risk for excessive drinking. The present study investigates the role of ß-endorphin in moderating free-choice consumption of ethanol in response to a blocked activity wheel. Female, transgenic mice with varying levels of the opioid peptide were given daily 2-h access to 20% ethanol with rotations on a running wheel blocked on alternate days. Subjects with low ß-endorphin exhibited enhanced stress sensitivity by self-administering larger quantities of ethanol on days when wheel running was prevented. ß-endorphin levels did not influence voluntary activity on the running wheel. There were genotypic differences in plasma corticosterone levels as well as corticotropin-releasing hormone mRNA content in multiple brain regions associated with the stress response in these free drinking and running subjects. Susceptibility to stress is enhanced in female mice with low levels of ß-endorphin, and better understanding of the role for this opioid in mitigating the response to stressors may aid in the development of interventions and treatments for excessive use of alcohol in women.