GABAergic neurons of the thalamic reticular nucleus (TRN) have critical roles in controlling sensory processing, in generating synchronous oscillations in thalamocortical networks, and in modulating attention. TRN neurons are rapidly activated by glutamatergic inputs that originate in both cortex and thalamus. In turn, they form powerful inhibitory connections with relay cells in several dorsal thalamic nuclei. TRN neuronal output is regulated by networks of local GABAergic synapses as well as by a system of cholinergic afferents that originate in the brainstem and basal forebrain. The long-term goal of this proposal is to better understand the complex roles TRN plays in regulating thalamic activity. The primary objective is to determine how distinct types of GABAergic and cholinergic synaptic inputs control the output of TRN neurons. The central hypothesis states that both GABAergic and cholinergic inputs can powerfully excite TRN neurons and that specific types of dendritically expressed voltage- and calcium gated conductances are involved in the integration of these inputs. The rationale for the proposed research is that understanding the mechanisms that underlie GABAergic and cholinergic signaling in the TRN will aid in revealing the principles underlying network activity in the TRN, ultimately translating into a better understanding of the specific processes leading to TRN dysfunction associated with a number of neurological diseases. Guided by strong preliminary data, the central hypothesis will be tested by three specific aims: 1) Determine the functional properties of GABAergic synaptic transmission in the TRN. Under this aim, both the mechanisms underlying GABA-evoked activation of TRN neurons as well as its functional consequences on relay cell activity will be examined. 2) Determine the functional role of dendritic voltage- and calcium activated conductances. Under this aim, the contribution of T- type calcium and SK potassium conductances for the processing of GABAergic synaptic inputs will be tested. 3) Determine the properties of cholinergic inputs to TRN. Under this aim, the dynamics underlying activation of postsynaptic nicotinic and muscarinic receptors by the release of endogenous acetylcholine in the TRN will be examined. This approach will lead to novel insights concerning synaptic transmission in the thalamus. The proposed research is significant, because it is expected to advance and expand understanding of how distinct synaptic inputs shape network activity in TRN.

Public Health Relevance

The thalamic reticular nucleus is a brain area critical for the processing of sensory inputs and for the regulation of attention. This proposal will determine how local GABAergic synapses and afferent cholinergic synaptic inputs regulate activity in TRN neurons. Results from these studies will help to identify novel therapeutic targets to treat neurological diseases associated with TRN dysfunction, such as absence seizures or schizophrenia.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
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Talley, Edmund M
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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Dasgupta, Rajan; Seibt, Frederik; Beierlein, Michael (2018) Synaptic Release of Acetylcholine Rapidly Suppresses Cortical Activity by Recruiting Muscarinic Receptors in Layer 4. J Neurosci 38:5338-5350
Hunt Jr, Albert J; Dasgupta, Rajan; Rajamanickam, Shivakumar et al. (2018) Paraventricular hypothalamic and amygdalar CRF neurons synapse in the external globus pallidus. Brain Struct Funct 223:2685-2698
Beierlein, Michael (2017) Fast Cholinergic Synaptic Transmission in the Mammalian Central Nervous System. Cold Spring Harb Protoc 2017:pdb.top095083
Dasgupta, Rajan; Seibt, Frederik; Sun, Yan-Gang et al. (2017) Examining Cholinergic Synaptic Signaling in the Thalamic Reticular Nucleus. Cold Spring Harb Protoc 2017:pdb.prot095836
Sun, Yan-Gang; Rupprecht, Vanessa; Zhou, Li et al. (2016) mGluR1 and mGluR5 Synergistically Control Cholinergic Synaptic Transmission in the Thalamic Reticular Nucleus. J Neurosci 36:7886-96
Beierlein, Michael (2014) Synaptic mechanisms underlying cholinergic control of thalamic reticular nucleus neurons. J Physiol 592:4137-45
Pita-Almenar, Juan Diego; Yu, Dinghui; Lu, Hui-Chen et al. (2014) Mechanisms underlying desynchronization of cholinergic-evoked thalamic network activity. J Neurosci 34:14463-74
Sun, Yan-Gang; Pita-Almenar, Juan D; Wu, Chia-Shan et al. (2013) Biphasic cholinergic synaptic transmission controls action potential activity in thalamic reticular nucleus neurons. J Neurosci 33:2048-59
Sun, Yan-Gang; Wu, Chia-Shan; Renger, John J et al. (2012) GABAergic synaptic transmission triggers action potentials in thalamic reticular nucleus neurons. J Neurosci 32:7782-90
Sun, Yan-Gang; Wu, Chia-Shan; Lu, Hui-Chen et al. (2011) Target-dependent control of synaptic inhibition by endocannabinoids in the thalamus. J Neurosci 31:9222-30