Recurrent activity propagates through labile ensembles in macaque dorsolateral prefrontal microcircuits.

Human and non-human primate studies clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions. It is thought that intracortical synaptic architectures within the dlPFC are the integral neurobiological substrate that gives rise to these processes. In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the "canonical" cortical microcircuit.

Impulsive Choices Emerge When the Anterior Cingulate Cortex Fails to Encode Deliberative Strategies.

Impulsive individuals excessively discount the value of delayed rewards, and this is thought to reflect deficits in brain regions critical for impulse control such as the anterior cingulate cortex (ACC). Delay discounting (DD) is an established measure of cognitive impulsivity, referring to the devaluation of rewards delayed in time. This study used male Wistar rats performing a DD task to test the hypothesis that neural activity states in ACC ensembles encode strategies that guide decision-making.

Neural basis of cognitive control signals in anterior cingulate cortex during delay discounting.

Cognitive control involves allocating cognitive effort according to internal needs and task demands and the Anterior Cingulate Cortex (ACC) is hypothesized to play a central role in this process. We investigated the neural basis of cognitive control in the ACC of rats performing an adjusting-amount delay discounting task. Decision-making in this this task can be guided by using either a lever-value tracking strategy, requiring a 'resource-based' form of cognitive effort or a lever-biased strategy requiring a 'resistance-based' form of cognitive effort.

Understanding How Acute Alcohol Impacts Neural Encoding in the Rodent Brain.

Alcohol impacts neural circuitry throughout the brain and has wide-ranging effects on the biophysical properties of neurons in these circuits. Articulating how these wide-ranging effects might eventually result in altered computational properties has the potential to provide a tractable working model of how alcohol alters neural encoding. This chapter reviews what is currently known about how acute alcohol influences neural activity in cortical, hippocampal, and dopaminergic circuits as these have been the primary focus of understanding how alcohol alters neural computation.

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 . 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 . In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the 'canonical' cortical microcircuit .

Repeated Binge Alcohol Drinking Leads to Reductions in Corticostriatal Theta Coherence in Female but not Male Mice.

Decreased functional connectivity between the striatum and frontal cortex is observed in individuals with alcohol use disorder (AUD), and predicts the probability of relapse in abstinent individuals with AUD. To further our understanding of how repeated alcohol (ethanol; EtOH) consumption impacts the corticostriatal circuit, extracellular electrophysiological recordings (local field potentials; LFPs) were gathered from the nucleus accumbens (NAc) and prefrontal cortex (PFC) of C57BL/6J mice voluntarily consuming EtOH or water using a 'drinking-in-the-dark' (DID) procedure. Following a three-day acclimation period wherein only water access was provided during DID, mice were given 15 consecutive days of access to EtOH.

Sex Differences in Neural Networks Recruited by Frontloaded Binge Alcohol Drinking.

Frontloading is an alcohol drinking pattern where intake is skewed toward the onset of access. The goal of the current study was to identify brain regions involved in frontloading. Whole brain imaging was performed in 63 C57Bl/6J (32 female and 31 male) mice that underwent 8 days of binge drinking using the drinking-in-the-dark (DID) model.

Neural Activity in the Anterior Insula at Drinking Onset and Licking Relates to Compulsion-Like Alcohol Consumption.

Much remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role of the anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from the AIC promote compulsion-like intake in rats and are recruited in heavy-drinking humans during compulsion for alcohol, highlighting the importance of and need for more information about AIC activity patterns that support aversion-resistant responding.

Non-Consummatory Behavior Signals Predict Aversion-Resistant Alcohol Drinking in Head-Fixed Mice.

A key facet of alcohol use disorder is continuing to drink alcohol despite negative consequences (so called "aversion-resistant drinking"). In this study, we sought to assess the degree to which head-fixed mice exhibit aversion-resistant drinking and to leverage behavioral analysis techniques available in head-fixture to relate non-consummatory behaviors to aversion-resistant drinking. We assessed aversion-resistant drinking in head-fixed female and male C57BL/6J mice.

Non-consummatory behavior signals predict aversion-resistant alcohol drinking in head-fixed mice.

A key facet of alcohol use disorder is continuing to drink alcohol despite negative consequences (so called "aversion-resistant drinking"). In this study, we sought to assess the degree to which head-fixed mice exhibit aversion-resistant drinking and to leverage behavioral analysis techniques available in head-fixture to relate non-consummatory behaviors to aversion-resistant drinking. We assessed aversion-resistant drinking in head-fixed female and male C57BL/6 J mice.

Flexible coding schemes in dorsomedial prefrontal cortex underlie decision-making during delay discounting.

Determining how an agent decides between a small, immediate versus a larger, delayed reward has provided insight into the psychological and neural basis of decision-making. The tendency to excessively discount the value of delayed rewards is thought to reflect deficits in brain regions critical for impulse control such as the prefrontal cortex (PFC). This study tested the hypothesis that dorsomedial PFC (dmPFC) is critically involved in flexibly managing neural representations of strategies that limit impulsive choices.

Distinct cortico-striatal compartments drive competition between adaptive and automatized behavior.

Cortical and basal ganglia circuits play a crucial role in the formation of goal-directed and habitual behaviors. In this study, we investigate the cortico-striatal circuitry involved in learning and the role of this circuitry in the emergence of inflexible behaviors such as those observed in addiction. Specifically, we develop a computational model of cortico-striatal interactions that performs concurrent goal-directed and habit learning.

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.

A critical review of front-loading: A maladaptive drinking pattern driven by alcohol's rewarding effects.

Front-loading is a drinking pattern in which alcohol intake is skewed toward the onset of reward access. This phenomenon has been reported across several different alcohol self-administration protocols in a wide variety of species, including humans. The hypothesis of the current review is that front-loading emerges in response to the rewarding effects of alcohol and can be used to measure the motivation to consume alcohol.

Compulsive alcohol drinking in rodents is associated with altered representations of behavioral control and seeking in dorsal medial prefrontal cortex.

A key feature of compulsive alcohol drinking is continuing to drink despite negative consequences. To examine the changes in neural activity that underlie this behavior, compulsive alcohol drinking was assessed in a validated rodent model of heritable risk for excessive drinking (alcohol preferring (P) rats). Neural activity was measured in dorsal medial prefrontal cortex (dmPFC-a brain region involved in maladaptive decision-making) and assessed via change point analyses and novel principal component analyses.

The rodent medial prefrontal cortex and associated circuits in orchestrating adaptive behavior under variable demands.

Emerging evidence implicates rodent medial prefrontal cortex (mPFC) in tasks requiring adaptation of behavior to changing information from external and internal sources. However, the computations within mPFC and subsequent outputs that determine behavior are incompletely understood. We review the involvement of mPFC subregions, and their projections to the striatum and amygdala in two broad types of tasks in rodents: 1) appetitive and aversive Pavlovian and operant conditioning tasks that engage mPFC-striatum and mPFC-amygdala circuits, and 2) foraging-based tasks that require decision making to optimize reward.

Effect of ketamine on binge drinking patterns in crossed high alcohol-preferring (cHAP) mice.

Background: Previous research has demonstrated the utility of subanesthetic doses of ketamine in decreasing binge (Drinking-in-the-Dark, or DID) 20% alcohol intake in female inbred (C57BL/6J) mice when administered 12 hours prior to alcohol access (Crowley et al., 2019). In the current study, we assess the efficacy of a similar ketamine pretreatment using male and female selectively bred, crossed High Alcohol Preferring (cHAP) mice, which also drink to intoxication, but are not inbred.

Understanding ethanol's acute effects on medial prefrontal cortex neural activity using state-space approaches.

Acute ethanol (EtOH) intoxication results in several maladaptive behaviors that may be attributable, in part, to the effects of EtOH on neural activity in medial prefrontal cortex (mPFC). The acute effects of EtOH on mPFC function have been largely described as inhibitory. However, translating these observations on function into a mechanism capable of delineating acute EtOH's effects on behavior has proven difficult.

Disruption of Long-Term Depression Potentiates Latent Inhibition: Key Role for Central Nucleus of the Amygdala.

Background: Latent inhibition (LI) reflects an adaptive form of learning impaired in certain forms of mental illness. Glutamate receptor activity is linked to LI, but the potential role of synaptic plasticity remains unspecified.

Methods: Accordingly, the present study examined the possible role of long-term depression (LTD) in LI induced by prior exposure of rats to an auditory stimulus used subsequently as a conditional stimulus to signal a pending footshock.

Impaired cognitive flexibility and heightened urgency are associated with increased alcohol consumption in rodent models of excessive drinking.

Alcohol use disorder (AUD) is characterized by impairments in decision-making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision-making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre-existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce.

Differential effects of quinine adulteration of alcohol on seeking and drinking.

Alcohol dependence is characterized by compulsive alcohol use. Alcohol-paired stimuli can drive compulsive alcohol use, induce craving, and lead to relapse. Alcohol dependence is highly heritable, and individuals with a family history are at elevated risk to develop an alcohol use disorder.

A Method to Present and Analyze Ensembles of Information Sources.

Information theory is a powerful tool for analyzing complex systems. In many areas of neuroscience, it is now possible to gather data from large ensembles of neural variables (e.g.

Ethanol Alters Variability, But Not Rate, of Firing in Medial Prefrontal Cortex Neurons of Awake-Behaving Rats.

Background: The medial prefrontal cortex (mPFC) is a brain region involved in the evaluation and selection of motivationally relevant outcomes. Neural activity in mPFC is altered following acute ethanol (EtOH) use and, in rodent models, doses as low as 0.75 g/kg yield cognitive deficits.

High Alcohol-Preferring Mice Show Reaction to Loss of Ethanol Reward Following Repeated Binge Drinking.

Background: Beyond yielding high blood ethanol (EtOH) concentrations (BECs), binge-drinking models allow examination of drinking patterns which may be associated with EtOH's rewarding effects, including front-loading and consummatory successive negative contrast (cSNC), a decrease in intake when only water is available to subjects expecting EtOH. The goals of the current study were to broaden our understanding of these reward-related behaviors during binge EtOH access in high alcohol-preferring (HAP) replicate lines (HAP2 and HAP3) of mice selectively bred to prefer alcohol. We hypothesized that both lines would show evidence of front-loading during binge EtOH access and that we would find a cSNC effect in groups where EtOH was replaced with water, as these results have been shown previously in HAP1 mice.