Bidirectional regulation of synaptic plasticity in the basolateral amygdala induced by the D1‐like family of dopamine receptors and group II metabotropic glutamate receptors. (5th September 2014)

• Record Type: Journal Article
• Authors: Li, Chenchen; Rainnie, Donald G.
• Is Part Of: Journal of physiology. Volume 592:Number 19(2014:Oct.)
• Page Start: 4329
• Page End: 4351
• Publication Date: 2014-09-05
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2014.277715
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Key points: Synaptic plasticity [long‐term potentiation (LTP) and long‐term depression (LTD) /depotentiation] in principal neurons of the basolateral amygdala (BLA) may underlie the acquisition, consolidation and extinction of fear memories, respectively. Dopamine‐dependent LTP and group II metabotropic glutamate (mGluR2 /3 ) receptor‐induced synaptic depotentiation in principal neurons of the BLA are thought to facilitate and attenuate fear memory formation, respectively. Here, we report that synaptic plasticity in BLA principal neurons is frequency‐dependent, with the transition from LTD to LTP occurring at stimulation frequencies at, or around, 10 Hz. Low frequency paired‐pulse stimulation (PP‐LFS) of afferents to the BLA elicits mGluR2 /3 receptor‐dependent LTD, whereas high frequency stimulation elicits D1 receptor‐dependent LTP. At intermediate frequencies, synaptic strength is stable due to co‐activation of both mGluR2 /3 and D1 signalling cascades. The temporal relationship of mGluR2 /3 and D1 signalling is highly relevant for synaptic plasticity, with pre‐application of D1 agonists blocking mGluR2 /3 receptor‐dependent synaptic depression and depotentiation. Characterization of the functional interactions between these two systems may not only provide important clues to link the hypothesized aberrant dopamine‐mediated molecular mechanisms and mGluR2 ‐related treatment to the pathophysiology of these psychiatric disorders, but also represent novel targets for anxiolytic pharmacotherapy in amygdala. Abstract: Competing mechanisms of long‐term potentiation (LTP) and long‐term depression (LTD) in principal neurons of the basolateral amygdala (BLA) are thought to underlie the acquisition and consolidation of fear memories, and their subsequent extinction. However, no study to date has examined the locus of action and/or the cellular mechanism(s) by which these processes interact. Here, we report that synaptic plasticity in the cortical pathway onto BLA principal neurons is frequency‐dependent and shows a transition from LTD to LTP at stimulation frequencies of ∼10 Hz. At the crossover point from LTD to LTP induction we show that concurrent activation of D1 and group II metabotropic glutamate (mGluR2/3 ) receptors act to nullify any net change in synaptic strength. Significantly, blockade of either D1 or mGluR2/3 receptors unmasked 10 Hz stimulation‐induced LTD and LTP, respectively. Significantly, prior activation of presynaptic D1 receptors caused a time‐dependent attenuation of mGluR2 /3 ‐induced depotentiation of previously induced LTP. Furthermore, studies with cell type‐specific postsynaptic transgene expression of designer receptors activated by designer drugs (DREADDs) suggest that the interaction results via bidirectional modulation of adenylate cyclase activity in presynaptic glutamatergic terminals. The results of our study raise the possibility that the temporal sequence of activation of either presynaptic D1 receptors or mGluR2/3 receptors may critically regulate the direction of synaptic plasticity in afferent pathways onto BLA principal neurons. Hence, the interaction of these two neurotransmitter systems may represent an important mechanism for bidirectional metaplasticity in BLA circuits and thus modulate the acquisition and extinction of fear memory.