Identification of the Hippocampal Input to Medial Prefrontal Cortex In Vitro

Abstract

To delineate the cellular mechanisms underlying the function of medial prefrontal cortex (mPFC) networks, it is critical to understand how synaptic inputs from various afferents are integrated and drive neuronal activity in this region. Using a newly developed slice preparation, we were able to identify a bundle of axons that contain extraneocortical fibers projecting to neurons in the prelimbic cortex. The anatomical origin and functional connectivity of the identified fiber bundle were probed by in vivo track tracing in combination with optic and whole-cell recordings of neurons in layers 2/3 and 5/6. We demonstrate that the identified bundle contains afferent fibers primarily from the ventral hippocampus but does not include contributions from the mediodorsal nucleus of the thalamus, amygdala, or lateral hypothalamus/medial forebrain bundle. Further, we provide evidence that activation of this fiber bundle results in patterned activity of neurons in the mPFC, which is distinct from that of laminar stimulation of either the deep layers 5/6 or the superficial layer 1. Evoked excitatory postsynaptic potentials are monosynaptic and glutamatergic and exhibit bidirectional changes in synaptic efficacy in response to physiologically relevant induction protocols. These data provide the necessary groundwork for the characterization of the hippocampal pathway projecting to the mPFC.

Hippocampal Network Connectivity and Activation Differentiates Post-Traumatic Stress Disorder From Generalized Anxiety Disorder

“…This connectivity pattern in general mirrors its anatomical connectivity predicted by animal work across a range of species, which may be linked to various aspects of motivated behavior (Groenewegen et al, 1996;Parent et al, 2010).…”

“…By contrast, in rodents the ventral third (anterior in primates (Amaral, 1987;Moser and Moser, 1998;Sasaki et al, 2004)) is involved in endogenous anxiety, through connections with the amygdala (Cenquizca and Swanson, 2007;Kishi et al, 2006), the bed nucleus of the stria terminalis (Cenquizca and Swanson, 2006), striatum, and the prelimibic and infralimbic areas of the medial prefrontal cortex that lie ventral to the anatomical targets of the dorsal hippocampus (ie, anterior cingulate cortex) (Groenewegen et al, 1996;Parent et al, 2010). As such, the hippocampus may be an important brain locus for understanding the similarities and differences among anxiety disorders.…”

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

“…This selective increase in activation of PFC neurons is known to be mediated primarily by inputs from the hippocampo-PFC pathway (Jodo, 2013;Jodo et al, 2005;Kamiyama et al, 2011;Thomases et al, 2014) where LTD is reduced and induction of LTP is enhanced (Kamiyama et al, 2011;Thomases et al, 2014). Previous studies reveal that mLTD in PFC is observed when specifically stimulating the hippocampo-prefrontal pathway (Lopes-Aguiar et al, 2013;Parent et al, 2010;Wang and Yuan, 2009). Thus, it is possible that loss of M 1 -mediated mLTD at the hippocampo-PFC synapse plays a major role in regulating PFC activation by hippocampal afferents under normal conditions, and that loss of this function contributes to the increased activation of the PFC and resultant behavioral outcomes of dysfunctional recognition memory and social interaction in this rodent model.…”

“…Muscarinic acetylcholine receptors (mAChRs) play important roles in regulating synaptic plasticity in the PFC and activation of mAChRs induces LTD at the hippocampo-PFC synapse (Lopes-Aguiar et al, 2013;Parent et al, 2010;Wang and Yuan, 2009). Interestingly, multiple studies suggest that cholinergic signaling is disrupted in schizophrenia patients and in animal models of schizophrenia (Berman et al, 2007;Dean et al, 2002;Scarr and Dean, 2009b;Zavitsanou et al, 2004).…”

Deficiency of Dgcr8 , a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex

“…Using chromosomal engineering, we generated a mouse model carrying a 1.3-Mb chromosomal deficiency (Df(16)A) on mouse chromosome 16, which is syntenic to the 22q11.2 1.5-Mb microdeletion [Df (16)A +/− mice] (3). The Df(16)A +/− mouse strain provided compelling evidence that microRNA (miRNA) dysregulation emerges as a result of the 22q11.2 microdeletion (3).…”