Project (1): Developmental impairment of synaptic plasticity in Slack knock-out mice
PI: Lucas Matt, Co-PI: Robert Lukowski
Co-worker: Thomas Pham, Jiaqi Yin
Learning and memory are thought to derive from synaptic plasticity which is the property of glutamatergic synapses to alter their efficiency by up- or down-regulating the density of postsynaptic AMPA receptors by endo- or exocytosis, respectively. Experimentally, we can determine the plasticity of hippocampal synapses as long-term potentiation (LTP) or long-term depression (LTD).
The sodium-activated potassium channel Slack (sequence like a calcium-activated K+-channel, KNa2.2, Slo2.2) modulates resting membrane potential and thus neuronal excitability levels. Slack is highly expressed in the hippocampus, a brain region crucial for the processing and consolidation of spatial memory. Slack knockout mice (Slack-/-) were found to display specific deficiencies in hippocampus-dependent memory, particularly in the reversal learning of previously acquired tasks, a learning paradigm associated with impaired hippocampal LTD.
Using field recordings of excitatory postsynaptic potentials (fEPSP) as well as whole-cell patch-clamp recordings from hippocampal pyramidal cells we investigate the underlying physiological defects leading to this phenotype. On a molecular level, this investigation is supported by state-of-the-art imaging and biochemical methods.