The Key Amygdala-Hippocampal Dialogue for Adaptive Fear Memory

For centuries, philosophical and clinical studies have emphasized a fundamental dichotomy between emotion and cognition, for instance between implicit/emotional memory and explicit/representative memory. However, in the last few decades, cognitive neuroscience has highlighted data indicating that emotion and cognition are in fact in close interaction and that reciprocal amygdalar-hippocampal influences underlie their mutual regulation. While supporting this view, the present chapter discusses experimental data indicating that the hippocampal and amygdalar systems not only regulate each other and their functional outcomes but also qualify specific emotional memory representations through specific activations and interactions. Specifically, we review consistent data unveiling a direct contribution of both the amygdala and septo-hippocampal system to the identification of the predictor of a threat in different situations of fear conditioning. Our suggestion is that these two brain systems and their interplay determine the selection of relevant emotional stimuli, thereby contributing to the adaptive value of emotional memory. Hence, beyond the mutual quantitative regulation of these two brain systems described so far, we propose that different configurations of the hippocampal-amygdalar network qualitatively impact the formation of memory representations, thereby producing either adaptive or maladaptive (e.g., PTSD-like) fear memories

Conflict between Threat Sensitivity and Sensation Seeking in the Adolescent Brain : Role of the Hippocampus, and Neurobehavioural Plasticity Induced by Pleasurable Early Enriched Experience

Adolescence is characterized both by the exacerbation of the experience of anxiety, fear or threat, on one hand, and by increased reward seeking (reward sensitivity) and risk taking on the other hand. The rise of these apparently opposite processes, i.e., threat-related anxiety and reward-related sensation seeking, seems to stem from a relatively decreased top-down inhibition of amygdala and striatal circuits by regulatory systems (e.g., prefrontal cortex, hippocampus) that mature later. The present commentary article aims to discuss recent related literature and focusses on two main issues: (i) the septo-hippocampal system (in particular the ventral hippocampus) might be a crucial region for the regulation of approach-avoidance conflict and also for the selection of the most appropriate responses during adolescence, and (ii) developmental studies involving early-life pleasurable-enriched experience (as opposed to early-life adversity) might be a useful study paradigm in order to decipher whether neuroplasticity induced by such experiences (for example, in the hippocampus and associated circuitry) may lead to better top-down inhibition and more "balanced" adolescent responses to environmental demands

The Combined Impact Of IgLON Family Proteins Lsamp And Neurotrimin On Developing Neurons And Behavioral Profiles In Mouse

Cell surface neural adhesion proteins are critical components in the complex orchestration of cell proliferation, apoptosis, and neuritogenesis essential for proper brain construction and behavior. We focused on the impact of two plasticity-associated IgLON family neural adhesion molecules, Neurotrimin (Ntm) and Limbic system associated membrane protein (Lsamp), on mouse behavior and its underlying neural development. Phenotyping neurons derived from the hippocampi of Lsamp−/−, Ntm−/− and Lsamp−/−Ntm−/− mice was performed in parallel with behavioral testing. While the anatomy of mutant brains revealed no gross changes, the Ntm−/− hippocampal neurons exhibited premature sprouting of neurites and manifested accelerated neurite elongation and branching. We propose that Ntm exerts an inhibitory impact on neurite outgrowth, whereas Lsamp appears to be an enhancer of the said process as premature neuritogenesis in Ntm−/− neurons is apparent only in the presence of Lsamp. We also show interplay between Lsamp and Ntm in regulating tissue homeostasis: the impact of Ntm on cellular proliferation was dependent on Lsamp, and Lsamp appeared to be a positive regulator of apoptosis in the presence of Ntm. Behavioral phenotyping indicated test-specific interactions between Lsamp and Ntm. The phenotypes of single mutant lines, such as reduced swimming speed in Morris water maze and increased activity in the elevated plus maze, were magnified in Lsamp−/−Ntm−/− mice. Altogether, evidence both from behavioral experiments and cultured hippocampal cells show combined and differential interactions between Ntm and Lsamp in the formation of hippocampal circuits and behavioral profiles. We demonstrate that mutual interactions between IgLON molecules regulate the initiation of neurite sprouting at very early ages, and even cell-autonomously, independent of their regulation of cell-cell adhesion

Reinforcement learning in intelligent control : a biologically-inspired approach to the relearning problem

Merged with duplicate record 10026.1/2240 on 08.20.2017 by CS (TIS)The increasingly complex demands placed on control systems have resulted in a need for intelligent control, an approach that attempts to meet these demands by emulating the capabilities found in biological systems. The need to exploit existing knowledge is a desirable feature of any intelligent control system, and this leads to the relearning problem. The problem arises when a control system is required to effectively learn new knowledge whilst exploiting still useful knowledge from past experiences. This thesis describes the adaptive critic system using reinforcement learning, a computational framework that can effectively address many of the demands in intelligent control, but is less effective when it comes to addressing the relearning problem. The thesis argues that biological mechanisms of reinforcement learning (and relearning) may provide inspiration for developing artificial intelligent control mechanisms that can better address the relearning problem. A conceptual model of biological reinforcement learning and relearning is presented, and the thesis shows how inspiration derived from this model can be used to modify the adaptive critic. The performance of the modified adaptive critic system on the relearning problem is investigated based on simulations of the pole balancing problem, and this is compared to the performance of the original adaptive critic system. The thesis presents an analysis of the results from these simulations, and discusses the significance of these results in terms of addressing the relearning problem

EFFECTS OF CHEMOGENETIC INHIBITION OF VENTRAL HIPPOCAMPAL GLUTAMATERGIC NEURONS ON ANXIETY-LIKE DEFENSIVITY IN MALE LONG-EVANS HOODED RATS

Previous research in rodents and humans has implicated the ventral hippocampus in regulating anxiety. However, many rodent studies examining ventral hippocampal neuronal pathways have utilized lesions that create nonspecific and/or nonreversible damage to the region. The present study sought to characterize the role of ventral hippocampal glutamatergic pyramidal neurons in modulating anxiety-like behavior during exposure to a variety of threatening stimuli. Five weeks prior to testing, male Long-Evans hooded rats received ventral hippocampal viral-vector infusions expressing either pAAV-CaMKIIα-hM4D-mCherry (DREADD) or pAAV-CaMKIIa-EGFP (GFP). DREADD transfection allowed for the specific, noninvasive and temporary inhibition of ventral hippocampal glutamatergic neurons immediately before threat presentation. Rats were evaluated for behaviors congruent with anxiety- or fear-like defensive states (e.g., freezing, risk assessment, avoidance, etc.) during testing in the elevated plus-maze and light-dark exploration test, or footshock-induced contextually conditioned fear, respectively. Analyses revealed a significant effect of DREADD inhibition that was dependent on the type of threat exposure. Specifically, compared to GFP controls, DREADD-induced silencing of ventral hippocampal glutamatergic neurons reduced anxiety-like behavior in the elevated plus-maze and light-dark test, without reliably affecting the expression of conditioned fear. The present results confirm that ventral hippocampal glutamatergic pyramidal neurons are recruited in rats during exposure to anxiety-inducing stimuli. These data add to a growing literature implicating the ventral hippocampus as a key region involved in modulating anxiety-like behaviors in rodents, primates and humans