Calcium Channels, Synaptic Plasticity, and Spatial Learning
Background. Presynaptic CaV2.1 channels initiate neurotransmission at synapses in the brain. They are regulated by binding of calmodulin to a bipartite regulatory site in the proximal C-terminal domain. During trains of stimuli, initial calcium binding to high-affinity EF hands 3 and 4 causes facilitation of the calcium current and subsequent calcium binding to low-affinity EF hands 1 and 2 causes inactivation. In cultured sympathetic neurons, transfected CaV2.1 channels induce short-term presynaptic plasticity that is blocked by the IM-AA mutation in their calmodulin regulatory site. We have developed an IM-AA mutant mouse line, in which presynaptic plasticity is impaired at hippocampal synapses. The deficit in presynaptic plasticity leads to altered excitation/inhibition ratio in hippocampal circuits, weakened long-term potentiation of synaptic transmission, and dramatically impaired spatial learning and memory.
Research Project. Our current experiments are aimed at understanding how the IM-AA mutation impairs spatial learning and memory at the cellular, circuit, and systems levels. We will use molecular and cellular biology, whole-cell voltage clamp, and synaptic physiology to probe the underlying mechanisms for the effects of the IM-AA mutation on short-term synaptic plasticity and long-term potentiation at synapses in the hippocampus. We will study the input-output relationships of neural circuits in the hippocampal slice. We will use tetrodes and optical probes to record circuit functions of the hippocampus in vivo in awake, behaving mice, including studies of hippocampal sharp waves and sharp-wave ripples. Based on these results, we will develop realistic neural models for the changes in cellular and circuit function that impair spatial learning and memory in IM-AA mice.
See Nanou et al, PNAS 2016, J Neurosci 2018; Neuron 2018
PhD in neuroscience or a related field.
Experience with electrophysiology including whole-cell voltage clamp and brain slice recordings is required.
Experience with stereotaxic methods and in vivo electrophysiological recording is also valuable.
Additional components of this position include general molecular and cellular biology, imaging and immunocytochemistry, and mouse genetics and husbandry.
Internal Number: PD nCaCh 1
About University of Washington
The University of Washington is a major biomedical research institution in Seattle, WA. It has leading research and teaching programs in all aspects of neuroscience.