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Section CELLULAR NEUROSCIENCE
ing toward the plasma membrane still remains poorly understood.
Using a new biochemical tool combined with photonic live imaging, we controlled and followed the dynamic secretion of tagged AMPAR subunits in cultured rat hippocampal neurons. We characterize AMPAR trafficking from the ER to the Golgi apparatus and from Golgi to the plasma membrane.
We analyze the characteristics of basal AMPAR transport. We studied the influence of synaptic plasticity in the intracellular transport of GluAl containing AMPAR. Since the scaffold protein SAP97 has been shown to be involved in the intracellular AMPARs traffic via its PDZ interaction with GluAl, we have studied its role in the GluAl vesicular trafficking. We show that an abolishment of the PDZ interaction between GluAl and SAP97 alters the GluAl vesicular trafficking. We are characterizing how interaction of GluAl with SAP97 can regulate the intracellular transport of AMPARs.
Extrasynaptic Protease, MMP-9 in Healthy and Diseased Mind
Leszek Kaczmarek*
Nencki Institute, Warsaw, Poland. * Presenting e-mail: l.kaczmarek@nencki.gov.pl
Matrix metalloproteinase 9, MMP-9 is an extracellularly operating enzyme that has been demonstrated as important regulatory molecule in control of synaptic plasticity, learning and memory. Either genetic or pharmacological inhibition of MMP-9 impairs late phase of long-term potentiation at various pathways, as well as appetitive and spatial memory formation, although aversive learning remains apparently intact in MMP-9 KO mice. MMP-9 is locally translated and released from the excitatory synapses in response to neuronal activity. Extrasynaptic MMP-9 is required for growth and maturation of the dendritic spines to accumulate and immobilize AMPA receptors, making the excitatory synapses more efficacious. Animal studies have implicated MMP-9 in such neuropsychiatric conditions, as e.g., epileptogenesis, autism spectrum disorders, development of addiction, and depression. In humans, MMP-9 appears to contribute to epilepsy, alcohol addiction, Fragile X Syndrome, schizophrenia and bipolar disorder. In aggregate, all those conditions may be considered as relying on alterations of dendritic spines/excitatory synapses and thus understanding the role played by MMP-9 in the synaptic plasticity may allow to elucidate the underpinnings of major neuropsychiatric disorders.
Spontaneous Neurotransmitter Release and Synaptic Plasticity
Elena Nosyreva*, Lisa M. Monteggia, and Ege T. Kavalali
Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390-9111, USA. * Presenting e-mail: elena.nosyreva@utsouthwestern.edu
Spontaneous neurotransmitter release is a salient feature of all presynaptic nerve terminals. Recent studies have shown that these action potential independent release events are essential regulators of synaptic homeostasis; in particular, they are involved in the maintenance of synaptic strength in terms of both presynaptic release rate and postsynaptic sensitivity. Moreover, there is growing evidence that postsynaptic receptors and signaling elements that respond to spontaneous release events diverge from those that respond to evoked release, suggesting a spatial segregation of these two forms of neurotransmission. We have previously shown that application of NMDA receptor antagonists - ketamine (20 |) and MK80l (l0 |M) at rest potentiates synaptic responses in the CA1 regions of rat and mouse hippocampus. This potentiation requires protein synthesis, brain-derived neurotrophic factor expression, eukaryotic elongation factor-2 kinase function, and increased surface expression of AMPA receptors. The same synaptic potentiation could be elicited by deplete neurotransmitter selectively from spontaneously recycling vesicles. In recent experiments, we found that this form of synaptic potentiation does not fully occlude subsequent long-term potentiation elicited by theta burst stimulation (100 Hz theta-burst protocol: 100 Hz, four pulses per burst; 15 bursts at 200 ms intervals). In these experiments, we could detect an additional ~20% increase in synaptic efficacy following ketamine mediated potentiation of responses (~30% above baseline). In this setting, theta burst stimulation alone could elicit up to ~50% potentiation above baseline. Taken together, these findings demonstrate that selective presynaptic impairment of spontaneous release, without alterations in evoked neurotransmission, is sufficient to elicit synaptic potentiation, which shows limited overlap with canonical long term potentiation elicited by repetitive activity.
OM&P
Opera Med Physiol 2016 Vol. 2 (S1) 9
