title: Bidirectional regulation of synaptic plasticity in the basolateral amygdala induced by the D1-like family of dopamine receptors and group II metabotropic glutamate receptors.
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.
authors.affiliation: Division of Behavioural Neuroscience & Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, 30329, USA Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, 30329, USA.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Behavioural Neuroscience & Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, 30329, USA Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, 30329, USA drainni@emory.edu.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Rainnie
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2
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