The long-term goal of the proposed research program is to understand the role of prefrontal limbic cortices in cognitive, mnemonic and emotional processes. Regionally distinct limbic and eulaminate prefrontal cortices have a different role in these functions. The objective of the proposed studies is to investigate the anatomic organization of a massive feedback system issued from prefrontal limbic and adjacent eulaminate cortices and distributed to the mediodorsal and midline thalamic nuclei and the amygdala. Our previous work indicates that prefrontal limbic and eulaminate cortices can be distinguished by their structure and pattern of interconnections: Eulaminate cortices project to limbic cortices primarily through their upper layers. In contrast, limbic cortices project to all eulaminate cortices primarily through their deep layers, suggesting a predominant role in feedback communication. Our working hypothesis is that feedback projections from the functionally distinct prefrontal limbic and eulaminate cortices to the thalamus and the amygdala have specific roles in mnemonic, emotional and cognitive processes associated with these structures. We will test this hypothesis by investigating: 1 - how prefrontal limbic cortices, in comparison with the eulaminate, parcel feedback projection neurons destined for the mediodorsal thalamic nucleus and those destined for neighboring cortices. 2- whether the organization of projection neurons from prefrontal cortices to the thalamus follows a general plan, or if it varies depending on the particular thalamic destination or cortical origin. 3- If prefrontal limbic and eulaminate cortices have a different anatomic relationship with the amygdala based on their respective roles in emotion and cognition. Populations of feedback projection neurons will be identified by different tracers and will be considered anatomically distinct if they are segregated in different layers or modules, or by their differential expression of a cytoskeletal marker. The proposed studies have important implications for understanding the dissociation of emotional from cognitive processes in mental diseases which affect the prefrontal cortices, in general, and their limbic component, in particular.
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