Information from somatosensory inputs converge in the thalamus before passing on to the cerebral cortex. As the last subcortical relay station before these inputs reach the cortex, the thalamus plays an important role in processing and gating sensory information. For example, the auditory and tactile stimuli from the surrounding environment that are relayed by the thalamus to the sensory cortex differ depending on whether one is awake or asleep. The basis for this dynamic information gating is the intrinsic firing patterns of thalamic neurons. Different firing patterns influence the thalamocortical circuitry and thalamic output to the cortex via the thalamocortical relay (TC) neurons. Although much is known about how various firing patterns are modulated in TC neurons, little is known of how the different firing patterns of the TC neurons affect synaptic transmission at their presynaptic boutons. I propose a series of experiments designed to determine how presynaptic terminals of the TC neurons translate firing patterns into neurotransmitter release. A combination of optical and electrophysiological techniques will be used to study the relationship between presynaptic calcium and synaptic transmission of TC neurons in mouse brain slices. I have developed a thalamic slice preparation that labels the presynaptic terminals of TC projections to the nucleus reticularis (nRt) with calcium indicator dyes. Using this preparation, presynaptic calcium fluorescence signals will be measured and characterized pharmacologically. By monitoring presynaptic calcium, this preparation will allow the identification of the calcium channels associated with synaptic transmission at the TC-nRT connection. Furthermore, the effects of neuromodulators and firing patterns on presynaptic calcium dynamics and the subsequent changes in synaptic strength will be elucidated. By studying how these synapses decode different firing patterns into neurotransmitter release, the mechanisms regulating the role of the thalamus as a selective information filter will be identified. Understanding these mechanisms would aid in the rational development of therapies for aberrant thalamic processes such as sleep disorders and generalized seizures.
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