Renewal of an Extinguished Behavior in the Context of a Preceding Response

Instrumental behavior chains are sequences of responses that minimally involve procurement behaviors that enable consumption. Recent studies suggest a fundamental role for context in controlling the acquisition and extinction of simple operant responding and instrumental behavior chains. Experiments on the extinction of behavior chains reveal that context affects procurement and consumption responding differently, such that procurement responding is directly affected by physical context changes, but consumption responding seems only to be affected by the amount of preceding procurement responding. Separately extinguished consumption responding renews when returned to the “context” of procurement preceding it. The present experiment was designed to determine the nature of this relationship. Rats learned two different discriminated heterogeneous chains in which a discriminative stimulus set the occasion for a procurement response (e.g., pulling a chain), which led to a second discriminative stimulus that occasion-set a consumption response (e.g., pressing a lever) that produced a food-pellet reinforcer. After learning both chains and performing them concurrently, both consumption responses were extinguished outside their respective chains. Consumption responding was only renewed when preceded by its associated procurement response and not when preceded by a procurement response that led to a different consumption response in acquisition. The results support the view that procurement is influenced by the physical context while consumption is controlled primarily by the response that precedes it in the chain. Theoretical and applied implications are discussed

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. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries

Anxiety, fear, panic: An approach to assessing the defensive behavior system across the predatory imminence continuum.

In order to effectively thwart predation, antipredator defensive behaviors must be matched to the current spatio-temporal relationship to the predator. We have proposed a model where different defensive responses are organized along a predatory imminence continuum (PIC). The PIC is a behavior system organized as a sequence of innately programmed behavioral modes, each representing a different interaction with the predator or threat. Ranging from low threat to predator contact, the PIC categorizes defense modes as pre-encounter, post-encounter, and circa-strike, corresponding to states of anxiety, fear, and panic, respectively. This experiment examined if the same significant stressor caused overexpression of all defensive responses along the PIC, including anxiety-like behavior, freezing, and panic-like responses. Female and male mice were exposed to acute stress that consisted of a series of ten pseudorandomly presented unsignaled footshocks (or no shocks). Mice were subsequently tested on a battery of tasks to assess stress effects on pre-encounter (anxiety-like), post-encounter (fear), and circa-strike (panic-like) behaviors. Results revealed that following stress, mice exhibited increased anxiety-like behavior shown through reduced average velocity within a modified open field. Furthermore, stressed mice showed increased fear following a single footshock in a new context as well as an increase in reactivity to white noise in the original stress context, with stressed mice exhibiting a more robust circa-strike-like response than controls. Therefore, significant stress exposure influenced the defensive states of anxiety, fear, and panic across the predatory imminence continuum. This research could therefore reveal how such responses become maladaptive following traumatic stress in humans

Conditional and unconditional components of aversively motivated freezing, flight and darting in mice.

Fear conditioning is one of the most frequently used laboratory procedures for modeling learning and memory generally, and anxiety disorders in particular. The conditional response (CR) used in the majority of fear conditioning studies in rodents is freezing. Recently, it has been reported that under certain conditions, running, jumping, or darting replaces freezing as the dominant CR. These findings raise both a critical methodological problem and an important theoretical issue. If only freezing is measured but rodents express their learning with a different response, then significant instances of learning, memory, or fear may be missed. In terms of theory, whatever conditions lead to these different behaviors may be a key to how animals transition between different defensive responses and different emotional states. In mice, we replicated these past results but along with several novel control conditions. Contrary to the prior conclusions, running and darting were primarily a result of nonassociative processes and were actually suppressed by associative learning. Darting and flight were taken to be analogous to nonassociative startle or alpha responses that are potentiated by fear. Additionally, associative processes had some impact on the topography of flight behavior. On the other hand, freezing was the purest reflection of associative learning. We also uncovered a rule that describes when these movements replace freezing: when afraid, freeze until there is a sudden novel change in stimulation, then burst into vigorous flight attempts. This rule may also govern the change from fear to panic

Temporally restricted dopaminergic control of reward-conditioned movements.

Midbrain dopamine (DA) neurons encode both reward- and movement-related events and are implicated in disorders of reward processing as well as movement. Consequently, disentangling the contribution of DA neurons in reinforcing versus generating movements is challenging and has led to lasting controversy. In this study, we dissociated these functions by parametrically varying the timing of optogenetic manipulations in a Pavlovian conditioning task and examining the influence on anticipatory licking before reward delivery. Inhibiting both ventral tegmental area and substantia nigra pars compacta DA neurons in the post-reward period had a significantly greater behavioral effect than inhibition in the pre-reward period of the task. Furthermore, the contribution of DA neurons to behavior decreased linearly as a function of elapsed time after reward. Together, the results indicate a temporally restricted role of DA neurons primarily related to reinforcing stimulus-reward associations and suggest that directly generating movements is a comparatively less important function

Temporally restricted dopaminergic control of reward-conditioned movements.

Midbrain dopamine (DA) neurons encode both reward- and movement-related events and are implicated in disorders of reward processing as well as movement. Consequently, disentangling the contribution of DA neurons in reinforcing versus generating movements is challenging and has led to lasting controversy. In this study, we dissociated these functions by parametrically varying the timing of optogenetic manipulations in a Pavlovian conditioning task and examining the influence on anticipatory licking before reward delivery. Inhibiting both ventral tegmental area and substantia nigra pars compacta DA neurons in the post-reward period had a significantly greater behavioral effect than inhibition in the pre-reward period of the task. Furthermore, the contribution of DA neurons to behavior decreased linearly as a function of elapsed time after reward. Together, the results indicate a temporally restricted role of DA neurons primarily related to reinforcing stimulus-reward associations and suggest that directly generating movements is a comparatively less important function