Generalization and discrimination of inhibitory avoidance differentially engage anterior and posterior retrosplenial subregions

IntroductionIn a variety of behavioral procedures animals will show selective fear responding in shock-associated contexts, but not in other contexts. However, several factors can lead to generalized fear behavior, where responding is no longer constrained to the conditioning context and will transfer to novel contexts.MethodsHere, we assessed memory generalization using an inhibitory avoidance paradigm to determine if generalized avoidance behavior engages the retrosplenial cortex (RSC). Male and female Long Evans rats received inhibitory avoidance training prior to testing in the same context or a shifted context in two distinct rooms; one room that had fluorescent lighting (Light) and one that had red LED lighting (Dark).ResultsWe found that animals tested in a light context maintained context-specificity; animals tested in the same context as training showed longer latencies to cross and animals tested in the shifted context showed shorter latencies to cross. However, animals tested in the dark generalized their avoidance behavior; animals tested in the same context and animals tested in the shifted context showed similarly-high latencies to cross. We next examined expression of the immediate early gene zif268 and perineuronal nets (PNNs) following testing and found that while activity in the basolateral amygdala corresponded with overall levels of avoidance behaviors, anterior RSC (aRSC) activity corresponded with learned avoidance generally, but posterior RSC (pRSC) activity seemed to correspond with generalized memory. PNN reduction in the RSC was associated with memory formation and retrieval, suggesting a role for PNNs in synaptic plasticity. Further, PNNs did not reduce in the RSC in animals who showed a generalized avoidance behavior, in line with their hypothesized role in memory consolidation.DiscussionThese findings suggest that there is differential engagement of retrosplenial subregions along the rostrocaudal axis to generalization and discrimination

Combined Effects of Binge Alcohol and Exercise on Intensity of Perineuronal Nets

Perineuronal Nets (PNNs) are lattice-like protein structures that surround the soma and processes of neurons in the extracellular matrix. PNNs have been known to exist for over a century and regulate two main functions: neuroplasticity and neuroprotection. The roles of neuroplasticity and protection are deeply involved with everyday life but are of key importance concerning specific behaviors such as alcohol consumption and exercise. While many people can consume alcohol without experiencing negative consequences that outweigh the positive experiences, there is still a necessity to understand the underlying neurological consequences of consuming alcohol regularly. Limited research indicates that the expression of PNNs increases after alcohol exposure and decreases with physical exercise in cortical regions (Chen et al., 2015; Reichelt et al., 2019; Smith et al., 2015). This increased expression of PNNs seems to indicate a restriction of plasticity from specific behaviors such as binge drinking and a possible neuroprotective effect against the immunological effects of alcohol. Comparatively, the reduction in expression of PNNs in the presence of exercise suggests an increase in neuroplasticity. However, research surrounding perineuronal nets has been sporadic in the methods for the analysis of these structures. This lack of clarity has led to difficulty in the interpretation of data from existing sources. Through the use of fluorescent staining, ImageJ, and PIPSQUEAK AI, a standardized methodological approach for the quantification of PNNs was further developed to analyze the interaction between variables such as binge alcohol consumption and exercise.Psychology, Department ofHonors CollegeBiology and Biochemistry, Department o

Fear Reduced Through Unconditional Stimulus Deflation is Behaviorally Distinct From Extinction and Differentially Engages the Amygdala

Background Context fear memory can be reliably reduced by subsequent pairings of that context with a weaker shock. This procedure shares similarities with extinction learning: both involve extended time in the conditioning chamber following training and reduce context-elicited fear. Unlike extinction, this weak-shock exposure has been hypothesized to engage reconsolidation-like processes that weaken the original memory. Methods We directly compared the weak-shock procedure with extinction using male and female Long Evans rats. Results Both repeated weak-shock exposure and extinction resulted in decreased context freezing relative to animals that received context fear conditioning but no subsequent context exposure. Conditioning with the weak shock was not enough to form a persistent context-shock association on its own, suggesting that the weak-shock procedure does not create a new memory. Weak-shock exposure in a new context can still reduce freezing elicited by the training context, suggesting that it reduces responding through a different process than extinction, which does not transcend context. Finally, reduced fear behavior produced through both extinction and weak-shock exposure was mirrored by reduced zif268 expression in the basolateral amygdala. However, only the weak-shock procedure resulted in changes in lysine-48 polyubiquitin tagging in the synapse of the basolateral amygdala, suggesting that this procedure produced long-lasting changes in synaptic function within the basolateral amygdala. Conclusions These results suggest that the weak-shock procedure does not rely on the creation of a new inhibitory memory, as in extinction, and instead may alter the original representation of the shock to reduce fear responding