Contributions of GABAergic and glutamatergic mechanisms to isoflurane-induced suppression of thalamic somatosensory information transfer

Abstract

Indications for a pivotal role of the thalamocortical network in producing the state of anesthesia have come from in vivo animal studies as well as imaging studies in humans. We studied possible synaptic mechanisms of anesthesia-induced suppression of touch perception in the rat's thalamus. Thalamocortical relay neurons (TCNs) receive ascending and descending glutamatergic excitatory inputs via NMDA and non-NMDA receptors (AMPAR) and are subjected to GABA(A)ergic inhibitory input which shapes the sensory information conveyed to the cortex. The involvement of these synaptic receptors in the suppressive effects of the prototypic volatile anesthetic isoflurane was assessed by local iontophoretic administration of receptor agonists/antagonists during extracellular recordings of TCNs of the ventral posteromedial nucleus responding to whisker vibration in rats anesthetized with isoflurane concentrations of approximately 0.9 vol.% (baseline) and approximately 1.9 vol.% (ISO high). ISO high induced a profound suppression of response activity reflected by a conversion of the sustained vibratory responses to ON responses. Administration of NMDA, AMPA, or GABA(A)R antagonists caused a reversal to sustained responses in 88, 94 and 88% of the neurons, respectively, with a recovery to baseline levels of response activity. The data show that the block of thalamocortical transfer of tactile information under ISO high may result from an enhancement of GABA(A)ergic inhibition and/or a reduction of glutamatergic excitation. Furthermore, they show that the ascending vibratory signals still reach the thalamic neurons under the high isoflurane concentration, indicating that this input is resistant to isoflurane while the attenuation of excitation may be brought about at the corticothalamic glutamatergic facilitatory input.

High-Frequency Whisker Vibration Is Encoded by Phase-Locked Responses of Neurons in the Rat's Barrel Cortex

“…This study was performed after approval of the Hamburg Administration of Health and Consumer Protection on 18 adult Wistar rats (400 g body weight) using methods reported previously in detail (Detsch et al, 1999;Vahle-Hinz et al, 2007). Anesthesia was induced by inhalation of isoflurane via a mask, a cannula was inserted into the trachea, and the lungs were mechanically ventilated with 1.5-2.0 vol% end-tidal isoflurane in 100% oxygen during the surgical preparation.…”

“…Using light carefully controlled isoflurane anesthesia, we show that S1 neurons of rats are readily able to phase lock to continuous highfrequency whisker vibrations above 100 Hz. In previous studies, such highfrequency phase locking may have been masked by suppressive effects of the anesthetics used (Detsch et al, 1999;Friedberg et al, 1999;Sceniak and MacIver, 2006;Vahle-Hinz et al, 2007).…”

“…The ascending transmission of signals appears to preserve precision of timing and high-frequency components of vibrissa movements in the principal trigeminal nucleus and the ventral posteromedial nucleus (VPM) of the thalamus (Vahle-Hinz and Gottschaldt, 1983;Deschênes et al, 2003;Vahle-Hinz et al, 2007). The picture seems completely different at the level of the barrel cortex [primary somatosensory cortex (S1)].…”

General Anesthesia and Human Brain Connectivity

“…Of note is that whole-brain connectivity of the thalamus and putamen was assessed during auditory and somatosensory stimulation, so the results may not parallel those obtained during resting conditions. Moreover, the effect of anesthetics on the thalamus may be indirect, driven by actions on the cortex or subcortical areas that project to the thalamus (Alkire et al, 2000Vahle-Hinz et al 2007).…”

Imaging Neurovascular Function and Functional Recovery after Stroke in the Rat Striatum Using Forepaw Stimulation

“…39 We did not detect thalamic activation, consistent with a prior study in rats. 36 The absence of thalamic activity could be because of the effect of isoflurane on suppressing thalamic activity 40 and/or regional dependence of neurovascular coupling. 41 Figure 4B.…”