Browsing by Author "Larkum, Matthew"
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Item Dopamine modulates synaptic plasticity in dendrites of rat and human dentate granule cells(2010) Hamilton, Trevor; Wheatley, Matthew; Sinclair, Barry; Bachmann, Madeline; Larkum, Matthew; Colmers, WilliamThe mechanisms underlying memory formation in the hippocampal network remain a major unanswered aspect of neuroscience. Although high-frequency activity appears essential for plasticity, salience for memory formation is also provided by activity in ventral tegmental area (VTA) dopamine projections. Here, we report that activation of dopamine D1 receptors in dentate granule cells (DGCs) can preferentially increase dendritic excitability to both high-frequency afferent activity and high-frequency trains of backpropagating action potentials. Using whole-cell patch clamp recordings, calcium imaging, and neuropeptide Y to inhibit postsynaptic calcium influx, we found that activation of dendritic voltage-dependent calcium channels (VDCCs) is essential for dopamine-induced long-term potentiation (LTP), both in rat and human dentate gyrus (DG). Moreover, we demonstrate previously unreported spike-timing–dependent plasticity in the human hippocampus. These results suggest that when dopamine is released in the dentate gyrus with concurrent high-frequency activity there is an increased probability that synapses will be strengthened and reward-associated spatial memories will be formed.Item Modulation of distal calcium electrogenesis by neuropeptide Y1 receptors inhibits neocortical long-term depression(2013) Hamilton, Trevor; Xapelli, Sara; Michaelson, Sheldon; Larkum, Matthew; Colmers, WilliamIn layer 5 neocortical pyramidal neurons, backpropagating action potentials (bAPs) firing at rates above a critical frequency (CF) induce supralinear Ca2+ influx and regenerative potentials in apical dendrites. Paired temporally with an EPSP, this Ca2+ influx can result in synaptic plasticity. We studied the actions of neuropeptide Y (NPY), an abundant neocortical neuropeptide, on Ca2+ influx in layer 5 pyramidal neurons of somatosensory neocortex in Sprague Dawley and Wistar rats, using a combination of somatic and dendritic intracellular recordings and simultaneous Ca2+ imaging. Ca2+ influx induced by trains of bAPs above a neuron's CF was inhibited by NPY, acting only at the distal dendrite, via Y1 receptors. NPY does not affect evoked synaptic glutamate release, paired synaptic facilitation, or synaptic rundown in longer trains. Extracellular Cs+ did not prevent NPY's postsynaptic effects, suggesting it does not act via either G-protein-activated inwardly rectifying K+ conductance (GIRK) or hyperpolarization-activated, cyclic nucleotide-gated channels. NPY application suppresses the induction of the long-term depression (LTD) normally caused by pairing 100 EPSPs with bursts of 2 bAPs evoked at a supracritical frequency. These findings suggest that distal dendritic Ca2+ influx is necessary for LTD induction, and selective inhibition of this distal dendritic Ca2+ influx by NPY can thus regulate synaptic plasticity in layer 5 pyramidal neurons.