Different functions have been suggested for the hippocampus and its subdivisions along both transversal and longitudinal axes. Expression of immediate-early genes (IEGs) has been used to map specific functions onto neuronal activity in different areas of the brain including the hippocampus (IEG imaging). Here we review IEG studies on hippocampal functional dissociations with a particular focus on the CA3 subregion. We first discuss the cellular functions of IEGs and the brain system interactions that govern their dynamic expression in hippocampal neurons to provide a more solid framework for interpreting the findings from IEG studies. We show the pitfalls and shortcomings of conventional IEG imaging studies and describe advanced methods using IEGs for imaging of neuronal activity or functional intervention. We review the current IEG evidence of hippocampal function, subregional-specific contribution to different stages of memory formation, systems consolidation, functional dissociation between memory and anxiety/behavioral inhibition along the septotemporal axis, and different neural network properties of hippocampal subregions. In total, IEG studies provide support for (1) the role of the hippocampus in spatial and contextual learning and memory, (2) its role in continuous encoding of ongoing experience, (3) septotemporal dissociations between memory and anxiety, and (4) a dynamic relationship between pattern separation and pattern completion in the CA3 subregion. In closing, we provide a framework for how cutting-edge IEG imaging and intervention techniques will likely contribute to better understanding of the specific functions of CA3 and other hippocampal subregions.
Hippocampus place cell discharge is an important model system for understanding cognition, but evidence is missing that the place code is under the kind of dynamic attentional control characterized in primates as selective activation of one neural representation and suppression of another, competing representation. We investigated the apparent noise ("overdispersion") in the CA1 place code, hypothesizing that overdispersion results from discharge fluctuations as spatial attention alternates between distal cues and local/self-motion cues. The hypothesis predicts that: (1) preferential use of distal cues will decrease overdispersion; (2) global, attention-like states can be decoded from ensemble discharge such that both the discharge rates and the spatial firing patterns of individual cells will be distinct in the two states; (3) identifying attention-like states improves reconstructions of the rat's path from ensemble discharge. These predictions were confirmed, implying that a covert, dynamic attention-like process modulates discharge on a ϳ1 s time scale. We conclude the hippocampus place code is a dynamic representation of the spatial information in the immediate focus of attention.
Investigations into the mechanisms of memory formation have abided by the central tenet of the consolidation theory-that memory formation occurs in stages which differ in their requirement for protein synthesis. The current most widely accepted hypothesis posits that new memories are encoded as neural activity-induced changes in synaptic efficacy, and stabilization of these changes requires de novo protein synthesis. However, the basic assumptions of this view have been challenged by concerns regarding the specificity of the methods used to support the claim. Studies on immediateearly genes (IEGs), in particular Arc, provide a distinct and independent perspective on the issue of the requirement of new protein synthesis in synaptic plasticity and memory consolidation. The IEG Arc and its protein are dynamically induced in response to neuronal activity, and are directly involved in synaptic plasticity and memory consolidation. Although we provide extensive data on Arc's properties to address the requirement of genomic and proteomic responses in memory formation, Arc is merely one element in a network of genes that interact in a coordinated fashion to serve memory consolidation. From gene expression and other studies, we propose the view that the stabilization of a memory trace is a continuous and ongoing process, which does not have a discrete endpoint and cannot be reduced to a single deterministic "molecular cascade". Rather, memory traces are maintained within metastable networks, which must integrate and update past traces with new ones. Such an updating process may well recruit and use many of the plasticity mechanisms necessary for the initial encoding of memory.
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