Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat

Abstract

The medial prefrontal cortex (mPFC) has been associated with diverse functions including attentional processes, visceromotor activity, decision making, goal directed behavior, and working memory. Using retrograde tracing techniques, we examined, compared, and contrasted afferent projections to the four divisions of the mPFC in the rat: the medial (frontal) agranular (AGm), anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) cortices. Each division of the mPFC receives a unique set of afferent projections. There is a shift dorsoventrally along the mPFC from predominantly sensorimotor input to the dorsal mPFC (AGm and dorsal AC) to primarily 'limbic' input to the ventral mPFC (PL and IL). The AGm and dorsal AC receive afferent projections from widespread areas of the cortex (and associated thalamic nuclei) representing all sensory modalities. This information is presumably integrated at, and utilized by, the dorsal mPFC in goal directed actions. In contrast with the dorsal mPFC, the ventral mPFC receives significantly less cortical input overall and afferents from limbic as opposed to sensorimotor regions of cortex. The main sources of afferent projections to PL/IL are from the orbitomedial prefrontal, agranular insular, perirhinal and entorhinal cortices, the hippocampus, the claustrum, the medial basal forebrain, the basal nuclei of amygdala, the midline thalamus and monoaminergic nuclei of the brainstem. With a few exceptions, there are few projections from the hypothalamus to the dorsal or ventral mPFC. Accordingly, subcortical limbic information mainly reaches the mPFC via the midline thalamus and basal nuclei of amygdala. As discussed herein, based on patterns of afferent (as well as efferent) projections, PL is positioned to serve a direct role in cognitive functions homologous to dorsolateral PFC of primates, whereas IL appears to represent a visceromotor center homologous to the orbitomedial PFC of primates.

Dopamine D1 Receptor Activation Rescues Extinction Impairments in Low-Estrogen Female Rats and Induces Cortical Layer-Specific Activation Changes in Prefrontal–Amygdala Circuits

“…This finding is consistent with the known connectivity distinctions between IL layers (Gabbott et al, 2005). Moreover, dopaminergic projections from the VTA to the PFC synapse predominantly in layer V (Hoover and Vertes, 2007), providing evidence for a potential dopaminergic role in extinction retrieval, even in the absence of pharmacological manipulation. We found that while IL-BLA circuit activity did not correlate with freezing in VEH-treated animals, SKF treatment resulted in diverging correlations between layer V activation and freezing behavior in PRO vs EMD animals.…”

Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

“…The layer V pyramidal neurons in ACd integrate widespread inputs from various brain regions (Hoover and Vertes, 2007) and project to multiple subcortical areas, including striatum, amygdala, dorsal raphe, and spinal cord (Gabbott et al, 2005), to facilitate emotional expression, motor coordination, and temporal organization of behavior. In adult mice with early-life stressful experiences and vehicle treatment, mPFC-dependent cognition, including certain aspects of attention (reflected by the percentage of same arm returns) and temporal order memory, was markedly impaired.…”

The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function

“…Projections originating in the perirhinal cortex and terminating in other cortical areas include the anterior cingulate, prelimbic, infralimbic, frontal, piriform, visual and parietal cortices (Saper, 1982;Naber et al, 1997;Burwell and Amaral, 1998a,b;Haberly, 2001;Hoover and Vertes, 2007;Agster and Burwell, 2009). Unlike the afferent projections of the perirhinal cortex, its efferents all involve both areas 35 and 36, albeit with some weighting towards one or the other in some cases (Burwell and Amaral, 1998a;McIntyre et al, 1996;Delatour and Witter, 2002;Agster and Burwell, 2009).…”

“…There are a number of return projections from the perirhinal cortex to the medial prefrontal cortex (Hoover and Vertes, 2007). Specifically, the perirhinal cortex projects to the anterior cingulate, prelimbic and infralimbic cortices Agster and Burwell, 2009).…”