State-Dependent Gating of Sensory Inputs by Zona Incerta

Abstract

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 the cholinergic reticular activating system, implicated in regulating states of arousal, modulates ZI activity. We show that stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and pedunculopontine tegmental) results in suppression of spontaneous firing of ZI neurons. Iontophoretic application of the cholinergic agonist carbachol to ZI neurons suppresses both their spontaneous firing and their vibrissae-evoked responses. We also found that carbachol application to an in vitro slice preparation suppresses spontaneous firing of neurons in the ventral sector of ZI (ZIv). Finally, we demonstrate that the majority of ZIv neurons contain parvalbumin and project to POm. Based on these results, we present the state-dependent gating hypothesis, which states that differing behavioral states-regulated by the brain stem cholinergic system-modulate ZI activity, thereby regulating the response properties of higher-order nuclei such as POm.

Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion

“…We obtained single-unit, electrophysiological recordings from urethane-anesthetized rats, as previously described [24,50,61]. Consistent with our previous findings after electrolytic lesions of the spinothalamic tract [13], SCI significantly increased both spontaneous and sensory-evoked responses of PO neurons, as evidenced by comparing peri-stimulus time histograms (Fig.…”

“…At least 45 days after SCI, rats were anesthetized with urethane and prepared for extracellular recordings as previously described [24,50]. We selected urethane because it has no, or negligible, effects on glutamatergic and gamma-aminobutryic acid (GABA)ergic transmission, and therefore produces only minimal disruption of signal transmission [51].…”

Cholinergic Regulation of the Posterior Medial Thalamic Nucleus

“…In vitro, carbachol presynaptically suppressed GABAergic inputs to POm neurons. We recently demonstrated that the cholinoceptive, GABAergic inputs to POm arise from the zona incerta (see following text; Trageser et al 2006).…”

“…We recently demonstrated that both spontaneous and vibrissae-evoked activity of ZI neurons are suppressed by cholinergic inputs from the brain stem reticular activating system (Trageser et al 2006). Because these cholinergic inputs are responsible for transitions between behavioral states, such as sleep and alertness (Steriade 2003), we suggested a statedependent gating hypothesis, where differing behavioral states-regulated by the brain stem cholinergic system-modulate ZI activity, thereby modulating the response properties of POm neurons.…”

“…The responses revealed by suppressing ZI are determined by direct inputs from the trigeminal nuclei because they are resistant to cortical inactivation (Lavallée et al 2005). Thus ZI regulates POm responses, determining whether POm functions as a first-order or a higher-order nucleus.We recently demonstrated that both spontaneous and vibrissae-evoked activity of ZI neurons are suppressed by cholinergic inputs from the brain stem reticular activating system (Trageser et al 2006). Because these cholinergic inputs are responsible for transitions between behavioral states, such as sleep and alertness (Steriade 2003), we suggested a statedependent gating hypothesis, where differing behavioral states-regulated by the brain stem cholinergic system-modulate ZI activity, thereby modulating the response properties of POm neurons.…”