Fred Helmstetter

The mechanisms underlying the transition from acute to chronic pain are unclear but may involve the persistence or strengthening of pain memories acquired in part through associative learning. Contextual cues, which comprise the environment in which events occur, were recently described as a critical regulator of pain memory; both male rodents and humans exhibit increased pain sensitivity in environments recently associated with a single painful experience. It is unknown, however, how repeated exposure to an acute painful unconditioned stimulus in a distinct context modifies pain sensitivity or the expectation of pain in that environment. To answer this question, we conditioned mice to associate distinct contexts with either repeated administration of a mild visceral pain stimulus (intraperitoneal injection of acetic acid) or vehicle injection over the course of 3 days. On the final day of experiments, animals received either an acid injection or vehicle injection prior to being placed into both contexts. In this way, contextual control of pain sensitivity and pain expectation could be tested respectively. When re-exposed to the noxious stimulus in a familiar environment, both male and female mice exhibited context-dependent conditioned analgesia, a phenomenon mediated by endogenous opioid signaling. However, when expecting the presentation of a painful stimulus in a given context, males exhibited conditioned hypersensitivity whereas females exhibited endogenous opioid-mediated conditioned analgesia. These results are evidence that pain perception and engagement of endogenous opioid systems can be modified through their psychological …

The ubiquitin proteasome system (UPS) is a primary mechanism through which proteins are degraded in cells. UPS activity in the dorsal hippocampus (DH) is necessary for multiple types of memory, including object memory, in male rodents. However, sex differences in DH UPS activation after fear conditioning suggest that other forms of learning may also differentially regulate DH UPS activity in males and females. Here, we examined markers of UPS activity in the synaptic and cytoplasmic fractions of DH and medial prefrontal cortex (mPFC) tissue collected 1 h following object training. In males, training increased phosphorylation of proteasomal subunit Rpt6, 20S proteasome activity, and the amount of PSD-95 in the DH synaptic fraction, as well as proteasome activity in the mPFC synaptic fraction. In females, training did not affect measures of UPS or synaptic activity in the DH synaptic fraction or in either mPFC …

The rat retrosplenial cortex (RSC) makes critical contributions to learning and memory but these contributions may not be uniform along its rostro-caudal axis. Previous work suggests that event-related and context-related information are differentially encoded by anterior and posterior RSC subregions. Here, we further test this idea using a procedure in which spatial/environmental cues (context) and discrete event memories are acquired separately. All animals received a 5-min pre-exposure to the training context 24 h before contextual fear conditioning where shock was delivered immediately upon being placed in the chamber. Rats were tested for memory for the context the next day. We found that optogenetic inhibition of cells in only the posterior RSC during the pre-exposure phase, when spatial information is encoded, reduced behavioral responding during the subsequent memory test. However, similar …

Microglia are critical for regulation of neuronal circuits that mature from adolescence to adulthood. The morphological complexity and process length of microglia can indicate different activation states. These states are sensitive to a variety of environmental and stress conditions. Microglia are sensitive to many factors that also regulate social behavior, and in turn, microglial manipulations can impact social function. Brief social isolation is one factor that can lead to robust social changes. Here, we explored the role of microglia in the effects of brief social isolation on social recognition memory. Using morphological measures of Iba1 to index microglial intensity, complexity, and process length, we identified different effects of brief isolation on microglial complexity in the basal region of the amygdala between adults and adolescents alongside overall increases in intensity of Iba1 in several cortical brain regions. Short …

Introduction to the Special Issue to Commemorate the Scientific Legacy of David J. Bucci. - Abstract - Europe PMC Sign in | Create an account https://orcid.org Europe PMC Menu About Tools Developers Help Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus Search life-sciences literature (43,211,007 articles, preprints and more) Search Advanced search Feedback This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text Introduction to the Special Issue to Commemorate the Scientific Legacy of David J. Bucci. Todd TP 1 , Leaton RN 2 , Helmstetter FJ 3 Author information Affiliations 1. Department of Psychological Science, University of Vermont, Burlington, VT, United States. (1 author) 2. Department of Psychological and …

Previous work investigating the role of the retrosplenial cortex (RSC) in memory formation has demonstrated that its contributions are not uniform throughout the rostro-caudal axis. While the anterior region was necessary for encoding CS information in a trace conditioning procedure, the posterior retrosplenial cortex was needed to encode contextual information. Using the same behavioral procedure, we tested if there was a similar dissociation during memory retrieval. First, we found that memory retrieval following trace conditioning results in increased neural activity in both the anterior and posterior retrosplenial cortex, measured using the immediate early gene zif268. Similar increases were not found in either RSC subregion using a delay conditioning task. We then found that optogenetic inhibition of neural activity in either subregion impairs retrieval of a trace, but not delay, memory. Together these results add to …

Heightened fear responding is characteristic of fear- and anxiety-related disorders, including post-traumatic stress disorder. Neural plasticity in the amygdala is essential for both initial fear learning and fear expression, and strengthening of synaptic connections between the medial geniculate nucleus (MgN) and amygdala is critical for auditory fear learning. However, very little is known about what happens in the MgN-amygdala pathway during fear recall and extinction, in which conditional fear decreases with repeated presentations of the auditory stimulus alone. In the present study, we found that optogenetic inhibition of activity in the MgN-amygdala pathway during fear retrieval and extinction reduced expression of conditional fear. While this effect persisted for at least two weeks following pathway inhibition, it was specific to the context in which optogenetic inhibition occurred, linking MgN-BLA inhibition to …

The retrosplenial cortex (RSC) is extensively interconnected with the dorsal hippocampus and has several important roles in learning and memory. Recent work has demonstrated that certain types of context-dependent learning are selectively impaired when the posterior, but not the anterior, region of the RSC is damaged, suggesting that the role of the RSC in memory formation may not be uniform along its rostro-caudal axis. The current experiments tested the idea that the anterior and posterior portions of the rat RSC contribute to different aspects of memory formation. We first confirmed that brief optogenetic inhibition of either the anterior or posterior RSC resulted in decreased local cellular activity as indexed by immediate early gene zif268 expression and that this decrease was restricted to the target region within RSC. We then found that silencing the anterior or posterior RSC during trace fear training trials had …