Determinants of Synaptic Integration in Cerebellar Neurons
Date
2013-05-10
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Abstract
The integration of synaptic inputs by neurons relies on protein channels that conduct specific ions. Cav3 calcium (Ca2+) channels can amplify excitatory postsynaptic potentials (EPSPs) while Ca2+-activated potassium (KCa) channels decrease EPSP amplitude. By comparison, inhibitory postsynaptic potentials (IPSPs) can activate hyperpolarization-activated (HCN) channels that generate a rebound excitatory current at the end of an inhibitory stimulus. This thesis examines how Cav3, KCa, and HCN channels control synaptic integration in cerebellar Purkinje cells and deep cerebellar nuclei (DCN) neurons. These two populations of neurons are central to cerebellar function and represent a dichotomy of synaptic processing, as Purkinje cells receive primarily excitatory inputs, while DCN neurons receive mainly inhibitory inputs.
I tested the hypothesis that Cav3-mediated Ca2+ current activates KCa channels to control the summation of parallel fibre EPSPs in Purkinje cells. Patch clamp recordings from in vitro slices of rat cerebellum showed that Cav3 current activates intermediate conductance KCa (KCa3.1) channels, which have previously never been found in central neurons. KCa3.1 channels are activated at hyperpolarized membrane voltages, due to an extended Cav3 channel window current, and suppress summation of low-frequency EPSPs. Dynamic clamp experiments and computer simulations revealed that the Cav3-KCa3.1 complex increases the signal-to-noise ratio for sensory-like parallel fibre inputs undergoing short-term facilitation by selectively suppressing background inputs.
In DCN neurons, I tested the hypothesis that Cav3 and HCN channels control the frequency and timing of rebound bursts following inhibition by IPSPs. The results demonstrate that Cav3 and HCN currents are activated during physiological levels of hyperpolarization and modulate rebound bursts. A novel model of a DCN neuron showed that Cav3 current is solely responsible for generation of the rebound burst, while HCN channels increase burst frequency and temporal precision.
Together, this research demonstrates how a novel Cav3-KCa3.1 channel complex participates in the processing of excitatory inputs, and identifies a new synergistic interaction between ion channels that enables processing of inhibitory inputs. These findings illustrate the importance of ion channel interactions for signal processing in the cerebellum, with far reaching implications for neural circuits throughout the brain.
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Neuroscience, Physiology
Citation
Engbers, J. D. (2013). Determinants of Synaptic Integration in Cerebellar Neurons (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25604