General anesthesia consists of five distinct components: analgesia, amnesia, unconsciousness, immobility, and blunted autonomic responsiveness [1, 2]. While the spinal cord is considered to be the anatomic substrate for anesthetic-induced immobility in response to noxious stimulation [3, 4], the anatomic foundations for the other components are less well established. The thalamus is a key integrative structure for somatosensory transmission  and, in particular, ascending nociceptive information processing [6, 7].
Excitatory input regulates the functional state of thalamic neurons, and such input is provided by both ascending activating systems in the brain stem and hypothalamus and the descending (corticothalamic) pathway . Corticothalamic axons outnumber thalamocortical axons by ~10-fold , and activation of this massive descending input depolarizes thalamic neurons, including thalamocortical relay neurons in the ventrobasal (VB) complex, facilitates relay spike transfer, and/or alters the response mode of thalamic relay neurons [10–18]. Inhibitory control of thalamocortical neurons in rodents is provided exclusively by GABAergic neurons in the reticular thalamic nucleus [8, 19], and such control is mediated by disynaptic (cortex to RTN to VB) and monosynaptic (RTN to VB) connections.
Propofol (2-6-di-isopropylphenol) is a widely used intravenous anesthetic with a distinct chemical structure, and is a potent allosteric modulator of GABAA receptors [20, 21]. Recent clinical findings have revealed possible sites of propofol-elicited anesthetic action in the human brain [22, 23]. During propofol-induced unconsciousness in humans, somatosensory-evoked neuronal activity in the cortex and the thalamus is markedly decreased [24, 25]. In vivo extracellular recordings have also demonstrated that propofol suppresses field potentials in the rat thalamus and cortex, with more prominent effects in the cortex . However, the cortical suppression may reflect anesthetic actions on projection neurons located elsewhere, especially in the thalamus [22, 27]. A significant limitation to the in vivo data from anesthetized animals is the use of "background anesthesia" (typically induced by urethane, sodium pentobarbital or a ketamine/xylazine combination) for baseline recordings; such "background anesthesia" makes it impossible to interpret the data subsequently obtained with the anesthetic(s) of interest .
Propofol modulates GABA-evoked currents in heterologously expressed GABAA receptors containing an α1, α2, α4, α5, α6, δ or γ2L subunit [29–37]. Behavioral studies suggest that the β3 subunit is important in mediating propofol-induced unconsciousness and immobility , while the β2 subunit may mediate sedation . Propofol potentiation of GABA-evoked currents in heterologously expressed GABAA receptors is independent of the β1 subunit .
Cumulative data from a number of studies using a variety of techniques (including electrophysiology, gene knockout, immunohistochemistry, immunoprecipitation, and ligand binding) suggest that VB neurons primarily express synaptic α1β2γ2 and α4β2γ2 and extrasynaptic α4β2δ GABAA receptors while RTN neurons are likely to preferentially express synaptic α3β3γ2 GABAA receptors, with denser GABA receptor expression in VB than in RTN [40–58]. These data further support the hypothesis that the thalamus represents an important anatomic target for propofol.
The thalamus is central to the processing and transfer of nearly all sensory information that ultimately reaches the cortex, with the exception of olfaction, whose signals pass to the cortex without thalamic relay. Clinical observations strongly suggest that thalamic neuronal circuits are important targets for propofol. The effects of propofol at the cellular and synaptic levels in the thalamus are largely unknown, however. Therefore, we investigated the effect of propofol on synaptic integration and action potential firing in response to corticothalamic pathway stimulation in thalamocortical relay neurons in brain slices, using both current- and voltage-clamp recording techniques. The results demonstrated that propofol inhibited VB neurons by potentiating GABAA-receptor chloride channel-mediated currents. Preliminary results have been published in abstract form