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Abstract:
The synaptic plasticity of the Hippocampal Formation (HF, which includes the dentate gyrus -DG-, CA3, CA2, CA1, subiculum, pre-parasubiculum and the entorhinal cortex -EC) is strongly influenced by neurotransmiters (presumably Dopaminergic -DA, Ventral Tegmental Area-VTA; Noradrenergic -NA, Locus Coeruleus-LC and Serotoninergic -5-HT, Raphe Nuclei- RN, respectively), (Otmakhova and Lisman, 1996; Katsuki et al., 1997), although the anatomical basis of the chemical modulation of memory in the HF is far from being understood.
The neuroanatomical connections between the brainstem and in the HF in the nonhuman primate are still unclear. Previous tracer studies showed retrogradely labeled neurons in the brainstem areas including the VTA, LC and RN, after deposits in the hippocampus (Amaral and Cowan, 1980), as well as in the EC (Insausti et al., 1987). In order to characterize the neurochemical nature of those projections, as well as their topographic and laminar differences, we studied comparatively the distribution on those substances in the HF using immunohistochemical techniques.
Immunohistochemistry for each DA (Tyrosine Hydroxylase, TH), NA (Dopamine Beta Hydroxylase -DBH-, and 5-HT) as well as double-immunohistochemical techniques using Alexa 488 (5-HT detection) and Alexa 568 (TH or DBH labeling) disclosed that:
• The polymorphic layer of the DG had fibers with the three neurotransmitters, whereas the molecular layer showed only TH and 5-HT immunolabeling, without double-stained processes.
• The pyramidal layer of CA3 showed denser 5-HT fiber labeling than TH; CA1 showed only scattered TH and 5-HT fibers, without double labeling profiles.
• The subiculum and presubiculum showed fibers immunoreactive for TH, SER and BHD in the molecular layer. No double-labeled TH-5HT or DBH-5HT fibers were seen.
• The superficial layers of the rostral EC (I and II) displayed TH- or 5-HT-labelled processes, while the most lateral subdivisions of EC (ELR/ELc) had TH- or DBH-positive fibers; they did not show co-localization.
The preferential location of these positive fibers in ELR/ELc is significant, as this portion of the EC receives abundant unimodal and polymodal sensory input and innervates the body and tail of the hippocampus, and therefore it might be an important step for the monoaminergic modulation memory consolidation. Our preliminary anatomical results suggest that the HF function may be modulated independently by monoaminergic neurotransmitters.