Preliminary Evidence for a Direct Projection of the Prefrontal Cortex to the Hippocampus in the Squirrel Monkey

Abstract

Unilateral partial ablations in the medial prefrontal cortex of six squirrel monkeys led to fiber degeneration which followed cingulate and uncinate routes to the hippocampal region. Degenerating fibers were observed primarily in the alvear, but also in the perforant, bundle. Preterminal and terminal debris was seen on basket cells of the stratum oriens and pyramidal cells within the stratum pyramidalis of CA _1–3, Since the prefrontal cortex has been shown to receive convergent sensory inputs from both external and internal milieu, this projection may represent the anatomical substrate for the essential influence of this information on the hippocampus proper, and also explain data which show the prefrontal cortex and hippocampus to be integrally related to mechanisms of learning and memory behavior.

The Hippocampal Formation of the Primate Brain

“…Another feature of the temporal lobe afferent input to the monkey hippocampal formation is that in addition to the perirhinal input, cortical afferents to the molecular layer of the subiculum originate in the proisocortex and even the neocortex (areas TH and TF) of the posterior parahippocampal gyrus (Van Hoesen et at., 1979) while there was no evidence for cortical inputs beyond the perirhinal area in the rat (Kosel et at., 1983). Additional neocortical inputs to the monkey hippocampal formation have also been reported to originate from the frontal lobe (Leichnetz and Astruc, 1975) and from area TE of the temporal lobe (Schwerdtfeger, 1979) but we have been unable to confirm these in our own material. In any case, since it is not possible to identify temporal lobe cortical areas in the rat that are likely to be homologous to areas TF and TH of the posterior parahippocampal gyrus and there is no evidence of cortical inputs beyond the perirhinal area in the rat, it is likely that this parahippocampal input constitutes a true species difference that may reflect the increased neocortical connectivity of the primate hippocampal formation.…”

Changes in CREB activation in the prefrontal cortex and hippocampus blunt ethanol-induced behavioral sensitization in adolescent mice

“…In fact, an increase in levels of pCREB in the PFC during acquisition of conditioned place preference induced by intra-lateral hypothalamus stimulation was counteracted by a decrease in its levels in the hippocampus (Haghparast et al, 2011). The existence of a direct pathway from the CA1 region of the hippocampus to the infralimbic area of the PFC represents a link between those two brain regions in mechanisms of learning and memory (Leichnetz and Astruc, 1975; Swanson, 1981; Férino et al, 1987; Fuster, 1991). …”

“…There is a clear connection between the PFC and the hippocampus. A direct pathway of communication from field CA1 of Ammon's horns to the infralimbic area of the PFC (Leichnetz and Astruc, 1975; Swanson, 1981; Férino et al, 1987) may represent the anatomical substrate of the relationship between PFC and hippocampus in mechanisms of learning and memory (Leichnetz and Astruc, 1975; Fuster, 1991). The prelimbic cortex is the PFC region where most of the hippocampal terminal fields are localized (Jay and Witter, 1991).…”

The Hippocampus as a Cognitive Map

“…The terminal sites include the stratum oriens, stratum radiatum and stratum lacunosum in the hippocampus proper, and the polymorph layer in the fascia dentata. Finally, Leichnetz and Astruc (1975) have demonstrated a direct projection in monkey from the medial prefrontal cortex to CA1 and CA3 localized within stratum oriens, stratum pyramidale, and stratum lacunosum/moleculare. This pathway courses through cingulate and uncinate approaches to the hippocampus, entering either through the alvear or perforant paths.…”

“…What was available suggested weak or uncertain inputs from the following cortical areas: (1) prefrontal and cingulate cortices via the cingulum bundle (Adey 1951, Adey and Meyer 1952, White 1959, Cragg 1965, McLardy 1971, Leichnetz and Astruc 1975) * * although Domesick (1969Domesick ( , 1970 has presented strong evidence that, in the rat at least, most of the fibres in this bundle are thalamo-cortical and end in cingulate cortex and presubiculum; Shipley (1974 has demonstrated a projection from the presubiculum to the dorsal and medial entorhinal cortex; * * * (2) temporal cortex (Cragg 1965); (3) parietal areas, either directly (Pandya and Kuypers 1969, Pandya and Vignolo 1969, Petras, 1971 or indirectly via the cingulate cortex (Cragg 1965) and the prepyriform cortex (Cragg 1961); (4) pyriform cortex . Niemer, Goodfellow and Speaker (1963) and McKenzie and Smith (1970) have obtained electrophysiological evidence of projections from large areas of the neocortex to hippocampus, perhaps via entorhinal areas, but the precise pathways were not studied.…”