Inhibiting dopamine reuptake blocks the induction of long-term potentiation and depression in the lateral entorhinal cortex of awake rats

Abstract

Synaptic plasticity in olfactory inputs to the lateral entorhinal cortex may result in lasting changes in the processing of olfactory stimuli. Changes in dopaminergic tone can have strong effects on basal evoked synaptic responses in the superficial layers of the entorhinal cortex, and the current study investigated whether dopamine may modulate the induction of long-term potentiation (LTP) and depression (LTD) in piriform cortex inputs to layer II of the lateral entorhinal cortex in awake rats. Groups of animals were pretreated with either saline or the selective dopamine reuptake inhibitor GBR12909 prior to low or high frequency stimulation to induce LTD or LTP. In saline-treated groups, synaptic responses were potentiated to 122.4+/-6.4% of baseline levels following LTP induction, and were reduced to 84.5+/-4.9% following induction of LTD. Changes in synaptic responses were maintained for up to 60min and returned to baseline levels within 24h. In contrast, induction of both LTP and LTD was blocked in rats pretreated with GBR12909. Dopaminergic suppression of synaptic plasticity in the entorhinal cortex may serve to restrain activity-dependent plasticity during reward-relevant behavioral states or during processing of novel stimuli.

Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

“…Long-term potentiation of cortical inputs to the superficial layers of the entorhinal cortex has been described in vivo [11–14] and in vitro [15, 16]. Stimulation patterns required to induce LTP tend to be more intense in the entorhinal cortex than in the hippocampus [12, 14], and we have also found that induction of LTD in the entorhinal cortex requires intense low-frequency stimulation [17, 18].…”

“…Because the entorhinal cortex receives highly processed inputs from sensory and association cortices and also provides the hippocampal region with much of its sensory input [6, 7], lasting changes in the strength of synaptic inputs to the entorhinal cortex could alter the manner in which multimodal cortical inputs are integrated, modulate the strength of transmission of specific patterns of sensory input within the hippocampal formation, and contribute to mnemonic function [8–11]. Determining the effective stimulation parameters and the intracellular signals that mediate synaptic plasticity in the entorhinal cortex should allow insight into basic mechanisms that contribute to the cognitive functions of the parahippocampal region.…”

Exposure to cues associated with palatable food reward results in a dopamine D2 receptor-dependent suppression of evoked synaptic responses in the entorhinal cortex

“…The synaptic suppression may weaken the functional impact of sensory inputs to the entorhinal cortex, but it might also serve to make active synaptic inputs relatively more salient in comparison to reduced spontaneous synaptic activity [18], or may reduce possible interference between extrinsic and intrinsic synaptic inputs in the service of protecting working memory representations or contributing to the storage of longer lasting representations [13,19-22,54]. In addition, activation of D 1 receptors with low concentrations of applied dopamine strengthens synaptic responses in vitro [5,16], suggesting that dopamine may at times facilitate the strength of olfactory inputs to the entorhinal cortex.…”

Cerebral morphology and dopamine D2/D3 receptor distribution in humans: A combined [18F]fallypride and voxel-based morphometry study

“…The hippocampus and parahippocampal region receives dense DA projections from midbrain nuclei and dopaminergic drugs can modulate synaptic activity and plasticity in this region. Specifically, increasing DA activity in this area reduces neuronal firing and suppresses synaptic plasticity (Caruana et al, 2007; Caruana and Chapman, 2008). Longitudinal studies have established that VBM is sensitive to learning induced changes in synaptic plasticity suggesting that VBM is sensitive to the fine microstructure of the brain (Ilg et al, 2008).…”