The persistence of long‐term potentiation in the projection from ventral hippocampus to medial prefrontal cortex in awake rats

Abstract

A potentially vital pathway in the processing of spatial memory is the pathway from ventral hippocampus to medial prefrontal cortex (vHPC-mPFC). To assess long-term potentiation (LTP) induction and maintenance across days in this pathway, the effects of several induction paradigms were compared in awake, freely moving rats. Two different high-frequency stimulation (HFS) protocols generated LTP lasting no longer than 1 week. However, after delivering HFS on three consecutive days, LTP lasted an average of 20 days, due mainly to the greater initial induction. Thus the pathway does not require extensive multi-day stimulation to induce LTP, as for other intra-neocortical pathways, but also it does not exhibit the extremely long-lasting and stable LTP previously observed in area CA1 and the dentate gyrus. By using bilaterally placed stimulating and recording electrodes, we found that HFS in one vHPC generated responses and LTP in the contralateral mPFC, even when the ipsilateral mPFC was inactivated by CNQX. We attribute this crossed response to a polysynaptic pathway from the vHPC to the contralateral mPFC. Finally, we found that repeated overnight exposure to an enriched environment also potentiated the vHPC-mPFC response, but this too was a transient effect lasting < 9 days, declining to baseline even before the enriched environment treatment was completed. Overall, these findings are consistent with the view that potentiation of vHPC-mPFC pathway may play a key role in promoting the hippocampus-mPFC interplay that, over days, leads to long-term storage in the frontal cortex of memories that are independent of the hippocampus.

NMDA-receptor-dependent plasticity in the bed nucleus of the stria terminalis triggers long-term anxiolysis

“…Further experiments are necessary to determine the molecular mechanisms by which in the absence of NMDA-Rs stimulation, HFS vSUB/CA1 triggers LTD vSUB/CA1 and potentiates LTD ILCx... Finally, we can not exclude that HFS vSUB/CA1 also triggers plasticity in the mPFC 23 or the basolateral amygdala 34 , but we provide behavioral evidence that vSUB/CA1-driven NMDA-R-dependent LTP in the amBNST triggers anxiolytic-like effects. This is in line with pioneer studies showing that changing the activity in the amBNST has a direct impact on the perception of aversive contextual stimuli 35 or production of stress hormones 5 .…”

“…This HFS vSUB/CA1 , originally described by Abraham et al . 22 , induced an extremely long-lasting (>8 days), robust and stable LTP in the projection from vSUB/CA1 to medial prefrontal cortex (mPFC) 23 . Here, we established that HFS vSUB/CA1 triggers input-specific neuroplastic changes in the BNST ( Fig.…”

“…To induce LTP, high-frequency stimulation protocol was performed in the vSUB/CA1 (HFS vSUB/CA1 ) at the same intensity used for baseline (0.2–1 mA). To avoid the confounding effect of epilepsy driven behavioral changes occurring in awake freely moving animals 23 , HFS was delivered in anesthetized animals. HFS vSUB/CA1 consisted in 50 trains (500 pulses at 400 Hz, 250 μs duration pulse) presented as bursts of five trains.…”

Alcohol‐dependent molecular adaptations of the NMDA receptor system

“…The NMDAR-dependent long-term potentiation (LTP) is the basis of synaptic plasticity (Malenka 2003;Mayford et al 2012), and is associated with (1) the forward trafficking of AMPARs, (Malinow & Malenka 2002), (2) de novo protein synthesis (Kasai et al 2010) and (3) enlargement of existing spines in addition to the formation of new spines (Matsuzaki et al 2004). The NMDAR-dependent LTP was initially described in the hippocampus but was later observed in various brain regions important for the development of AUD, including the ventral tegmental area, the nucleus accumbens (NAc), the dorsal striatum, the prefrontal cortex (PFC) and amygdala (Bernier et al 2011;Britt et al 2012;Cho et al 2012;Taylor et al 2016;Wang et al 2012).…”

Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a streptozotocin model of Alzheimer’s disease

“…Limbic-cortical synaptic plasticity can be dysfunctional in prodromal Alzheimer's disease, which could explain its mild cognitive alterations (Scheff et al, 2006;Arendt, 2009). In this context, the hippocampal CA1-medial prefrontal cortex (mPFC) communication is prone to long-term plasticity (Lopes-Aguiar et al, 2008Takita et al, 2013), is implicated in working memory (Spellman et al, 2015;Blot et al, 2015) and memory consolidation (Laroche et al, 2000;Taylor et al, 2016;Maingret et al, 2016;Jadhav et al, 2016;Barker et al, 2017). Thus, synaptic plasticity in this circuit could be increasingly altered as Alzheimer's disease develops, which can be experimentally studied using the icv-STZ model of sAD.…”