Hippocampal afferents to the rat prefrontal cortex: Synaptic targets and relation to dopamine terminals

Abstract

Afferents to the prefrontal cortex (PFC) from the hippocampal formation and from midbrain dopamine (DA) neurons have been implicated in the cognitive and adaptive functions of this cortical region. In the present study, we investigated the ultrastructure and synaptic targets of hippocampal terminals, as well as their relation to DA terminals within the PFC of adult rats. Hippocampal afferents were labeled either by anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from the ventral hippocampal formation or by anterograde degeneration following fimbria lesion. Hippocampal terminals in the PFC, identified by either method, formed primarily asymmetric axospinous synapses, with a small percentage forming asymmetric axodendritic synapses. Dopamine terminals in the PFC were identified by peroxidase immunocytochemistry for either tyrosine hydroxylase or DA and formed primarily symmetric synapses onto dendritic spines and small caliber dendritic shafts. Spines that received symmetric synaptic contact from DA terminals invariably also received an asymmetric synapse from an unlabeled terminal, forming a triadic complex. Hippocampal and DA terminals in the PFC were not often observed in the same area of the neuropil, and no examples of convergence of hippocampal and DA terminals onto common postsynaptic targets were observed. Further analysis revealed that spines receiving synaptic contact from hippocampal terminals did not receive additional synaptic contact from any other source. However, when localized to the same area of the neuropil, hippocampal and DA terminals were often in direct apposition to one another, without forming axo-axonic synapses. These results suggest that 1) hippocampal terminals primarily form excitatory synapses onto spiny pyramidal neurons, 2) hippocampal afferents are unlikely to be synaptically modulated by DA or non-DA terminals at the level of the dendritic spine, and 3) appositions between hippocampal and DA terminals may facilitate presynaptic interactions between these afferents to the PFC.

Dopaminergic signaling in dendritic spines

“…A significant subpopulation of spines [15] is simultaneously contacted by both dopaminergic and glutamatergic varicosities [15][16], forming the "striatal microcircuit" or "synaptic triad" [17]. Similar DA innervation architecture is also observed in pyramidal neurons in the cortex and hippocampus, and magnocellualar neurons of basolateral amygdale [17,32]. This "triad" architecture can serve as a heterosynaptic co-incidence detector by which activation of the DA terminal selectively influences the simultaneously active converging glutamatergic input at the level of individual spines.…”

The hippocampus participates in a pharmacological rat model of absence seizures

“…Intrinsic resonance of hippocampal pyramidal cells at 4-10 Hz (Leung and Yu, 1998) or a decrease in inhibition (Perez Velazquez et al, 2007) may enhance the response to rhythmic excitation. The hippocampus, in turn, can activate specific thalamic and cortical areas, possibly indirectly through the prefrontal and cingulate cortex, midline thalamus or mesopontine brainstem (Carr and Sesack, 1996;Vertes et al, 2007;Leung et al, 2014).…”

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

“…What is the actual localization of these NMDA receptors and the source of the cortical hyperglutamatergic transmission induced by their blockade? Two of the well-known ascending glutamatergic inputs to the mPFC arise from the hippocampus (Carr and Sesack, 1996;Dégenètais et al, 2003) and the mediodorsal nucleus of the thalamus (Kuroda et al, 1998), and in both areas glutamatergic neurons are under the control of GABAergic cells (Gigg et al, 1994; Number of animals is given in parentheses. The control group received two injections (saline and vehicle) and, for the sake of clarity, is depicted as a dotted line.…”