| Description |
The human brain constantly undergoes changes that enable us to learn, form memories and make decisions. Abnormalities in the brain’s ability to undergo these changes underlie complex psychiatric disorders such as schizophrenia, autism spectrum disorders (ASD), post-traumatic stress disorder and Alzheimer’s disease. It is well established that long-term potentiation (LTP) of synaptic strength is the cellular correlate of learning and memory in various brain regions including the hippocampus
and the basolateral amygdala (BLA). These brain regions play key roles in contextual information processing and emotional learning respectively. Two types of neurons are present in these regions-
the excitatory principal cells and the inhibitory interneurons, both of which are important for learning and memory.
The first part of this seminar will focus on the molecular mechanisms underlying the insertion of synaptic AMPA receptors (AMPARs) triggered by activation of NMDA receptors, which is essential for LTP in the principal cells of the hippocampal CA1 region. We show that complexin, a protein that regulates neurotransmitter release at the presynaptic terminal, is also essential for the SNARE dependent exocytosis of synaptic AMPARs during LTP, but not for maintaining basal synaptic
strength. This regulated postsynaptic AMPAR exocytosis requires binding of complexin to SNARE complexes. In forebrain neurons, complexin acts together with synaptotagmin-1 to mediate presynaptic neurotransmitter release, but we find that synaptotagmin-1 is not required for
complexin-dependent AMPAR insertion during LTP. These results suggest a new complexin- dependent molecular mechanism for regulating AMPAR delivery to synapses, a mechanism that is surprisingly similar to presynaptic exocytosis but one that is controlled by distinct regulators.
The second part will focus on the on the role of interneurons in the basolateral amygdala where synaptic inputs to some interneurons have been shown to undergo synaptic plasticity, but the identity of these cells and the mechanisms that underlie this plasticity are not known. We show that LTP is restricted to a specific type of interneurons that are defined by the lack of expression of NR2B subunits in their NMDA receptors. We find that LTP is only present at cortical inputs to these cells and is initiated by calcium influx via calcium permeable AMPA receptors. LTP is maintained by trafficking of GluR2-lacking AMPA receptors that requires the actin cytoskeleton and SAP97. These results
define a novel population of interneurons in the BLA that control principal neuron excitability by cortical inputs. This selective enhanced inhibition contributes to reducing the activity of principal
neurons engaged during fear extinction.
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