Minibox: Custom solo or semi-group housing chambers for long term housing of rats with miniscopes.

In this detailed procedure, we include open-source methodologies using 'solidworks' designs for creating solo or semi-group housing units for rats wearing miniscopes for long periods of time. Builds are optimized to preserve rat health and prevent hardware destruction. We include all prices and suggestions for purchasing strategies to reduce overall build-costs.•Chambers are optimized for long-term housing to protect rats wearing delicate headstages (e.g., miniscopes).•Designed to be low-cost, efficient supplement to operant chambers and provides numerous benefits to long-term miniscope imaging. The housing chambers can be augmented by installing cameras, commutators, or different types of floor grids depending on experimental conditions.•The chambers can also be secured to one another to create "rat-duplexes", allowing experimenters to control the degree of social isolation.

Examining a punishment-related brain circuit with miniature fluorescence microscopes and deep learning.

In humans experiencing substance use disorder (SUD), abstinence from drug use is often motivated by a desire to avoid some undesirable consequence of further use: health effects, legal ramifications, etc. This process can be experimentally modeled in rodents by training and subsequently punishing an operant response in a context-induced reinstatement procedure. Understanding the biobehavioral mechanisms underlying punishment learning is critical to understanding both abstinence and relapse in individuals with SUD. To date, most investigations into the neural mechanisms of context-induced reinstatement following punishment have utilized discrete loss-of-function manipulations that do not capture ongoing changes in neural circuitry related to punishment-induced behavior change. Here, we describe a two-pronged approach to analyzing the biobehavioral mechanisms of punishment learning using miniature fluorescence microscopes and deep learning algorithms. We review recent advancements in both techniques and consider a target neural circuit.

Infralimbic cortex plays a similar role in the punishment and extinction of instrumental behavior.

Learning to stop responding is a fundamental process in instrumental learning. Animals may learn to stop responding under a variety of conditions that include punishment-where the response earns an aversive stimulus in addition to a reinforcer-and extinction-where a reinforced response now earns nothing at all. Recent research suggests that punishment and extinction may be related manifestations of a common retroactive interference process. In both paradigms, animals learn to stop performing a specific response in a specific context, suggesting direct inhibition of the response by the context. This process may depend on the infralimbic cortex (IL), which has been implicated in a variety of interference-based learning paradigms including extinction and habit learning. Despite the behavioral parallels between extinction and punishment, a corresponding role for IL in punishment has not been identified. Here we report that, in a simple arrangement where either punishment or extinction was conducted in a context that differed from the context in which the behavior was first acquired, IL inactivation reduced response suppression in the inhibitory context, but not responding when it "renewed" in the original context. In a more complex arrangement in which two responses were first trained in different contexts and then extinguished or punished in the opposite one, IL inactivation had no effect. The results advance our understanding of the effects of IL in retroactive interference and the behavioral mechanisms that can produce suppression of a response.

Response-specific effects of punishment of a discriminated operant response.

To determine whether the punishment of a discriminated operant behavior has effects that are specific to the punished response, rats were reinforced for performing two different instrumental responses (lever pressing and chain pulling) in the presence of a single discriminative stimulus (S). They were then either punished with mild footshock for performing one of the responses (R1) in S, or they received the same shocks in a noncontingent manner while performing R1 in S (i.e., a yoked control). In final tests of both R1 and R2 in S, the punished rats were more suppressed to R1 than R2, but the yoked rats were not. The results extend previous results with extinction rather than punishment learning (Bouton, Trask, & Carranza-Jasso, 2016) and support a larger parallel between extinction and punishment of both free-operant and discriminated-operant responding. Punishment is like extinction in creating a response-specific inhibition of either free or discriminated operant behavior.

Early-life seizures alter habit behavior formation and fronto-striatal circuit dynamics.

Obsessive compulsive disorder (OCD) can occur comorbidly with epilepsy; both are complex, disruptive disorders that lower quality of life. Both OCD and epilepsy are disorders of hyperexcitable circuits, but it is unclear whether common circuit pathology may underlie the co-occurrence of these two neuropsychiatric disorders. Here, we induced early-life seizures (ELS) in rats to examine habit formation as a model for compulsive behaviors. Compulsive, repetitive behaviors in OCD utilize the same circuitry as habit formation. We hypothesized that rats with ELS could be more susceptible to habit formation than littermate controls, and that altered behavior would correspond to altered signaling in fronto-striatal circuits that underlie decision-making and action initiation. Here, we show instead that rats with ELS were significantly less likely to form habit behaviors compared with control rats. This behavioral difference corresponded with significant alterations to temporal coordination within and between brain regions that underpin the action to habit transition: 1) phase coherence between the lateral orbitofrontal cortex and dorsomedial striatum (DMS) and 2) theta-gamma coupling within DMS. Finally, we used cortical electrical stimulation as a model of transcranial magnetic stimulation (TMS) to show that temporal coordination of fronto-striatal circuits in control and ELS rats are differentially susceptible to potentiating and suppressive stimulation, suggesting that altered underlying circuit physiology may lead to altered response to therapeutic interventions such as TMS.

Learning to stop responding.

Learning to stop responding is an important process that allows behavior to adapt to a changing and variable environment. This article reviews recent research in this laboratory and others that has studied how animals learn to stop responding in operant extinction, punishment, and feature-negative learning. Extinction and punishment are shown to be similar in two fundamental ways. First, the response-suppressing effects of both are highly context-specific. Second, the response-suppressing effects of both can be remarkably response-specific: Inhibition of one response transfers little to other responses. Learning to inhibit the response so specifically may result from the correction of "response error," the difference between the level of responding and what the current reinforcer supports. In contrast, the inhibition of responding that develops in feature-negative learning, where the response is reinforced during one discriminative stimulus (A) but not in a compound of A and stimulus B, is less response-specific: The inhibition of responding by stimulus B transfers and inhibits a second response, especially if the second response has itself been inhibited before. The results thus indicate both response-specific and response-general forms of behavioral inhibition. One possibility is that response-specific inhibition is learned when the circumstances encourage the organism to pay attention to the response-to what it is actually doing-as behavioral suppression is learned.

A comparison of renewal, spontaneous recovery, and reacquisition after punishment and extinction.

Punishment and extinction are both effective methods of reducing instrumental responding and may involve similar learning mechanisms. To characterize the similarities and differences between them, we examined three well-established recovery or "relapse" effects -renewal, spontaneous recovery, and reacquisition - following either punishment or extinction of an instrumental response. In Experiment 1a, both punished and extinguished responses renewed to similar degrees following a context change at test (ABA renewal). In Experiment 1b, responding spontaneously recovered to similar degrees following punishment or extinction. In Experiment 2, responding was rapidly reacquired when the response was reinforced again following extinction but not following punishment, as predicted by the idea that the reinforcer delivered in reacquisition is part of the context of punishment, but not extinction. The results collectively suggest that both punishment and extinction produce similar context-dependent retroactive interference effects. More broadly, they also suggest that punished and extinguished responses may be equally likely to return following a change of context despite the intuition that punishment might provide a more extreme and effective means of suppressing behavior. To our knowledge, this is the first direct behavioral comparison of response recovery after punishment and extinction within individual experiments.

Unexpected food outcomes can return a habit to goal-directed action.

Three experiments examined the return of a habitual instrumental response to the status of goal-directed action. In all experiments, rats received extensive training in which lever pressing was reinforced with food pellets on a random-interval schedule of reinforcement. In Experiment 1, the extensively-trained response was not affected by conditioning a taste aversion to the reinforcer, and was therefore considered a habit. However, if the response had earned a new and unexpected food pellet during the final training session, the response was affected by taste aversion conditioning to the (first) reinforcer, and had thus been converted to a goal-directed action. In Experiment 3, 30 min of prefeeding with an irrelevant food pellet immediately before the test also converted a habit back to action, as judged by the taste-aversion devaluation method. That result was consistent with difficulty in finding evidence of habit with the sensory-specific satiety method after extensive instrumental training (Experiment 2). The results suggest that an instrumental behavior's status as a habit is not permanent, and that a habit can be returned to action status by associating it with a surprising reinforcer (Experiment 1) or by giving the animal an unexpected prefeeding immediately prior to the action/habit test (Experiment 3).