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1 Program in Neuroscience, Dept. of Anatomy and Neurobiology, Univ. of Maryland School of Medicine, Baltimore, Maryland, United States
2 Dept. of Anatomy and Neurobiology, Univ. of Maryland School of Medicine, Program in Neuroscience, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: akeller{at}umaryland.edu.
We have previously shown that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incerto-thalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brainstem cholinergic system which regulates sleep/wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brainstem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Micro-iontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of mIPSCs, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brainstem cholinergic system, modulate the flow of information through POm.
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