Research reportIsoflurane induces dose-dependent changes of thalamic somatosensory information transfer
Introduction
Somatosensory information provided by cutaneous mechanoreceptors comprises the location, intensity, duration and velocity of skin indentation or movement of hairs. These stimulus parameters are conveyed by the different types of slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors. The sinus hair (whisker) follicles in rodents contain all types of mechanoreceptors also present in the human skin. The sinus hair system in rats, therefore, has been used as an experimental model for studies of the sensory discriminative aspects of touch. The stages of the ascending pathway consist of the trigeminal nerve and ganglion (first order neurons), the trigeminal sensory nuclei of the brainstem (second order neurons), the ventrobasal complex of the thalamus (VB, third order neurons) as well as the somatosensory cortex (Fig. 1A) 43, 48.
At the thalamic level, the mechanoreceptors of the body surface are represented in topological order within the subnuclei of the VB, i.e., the ventral posteromedial (VPM: representation of the head) and ventral posterolateral nuclei (VPL: representation of the trunk and limbs) [21]. The neurons of the VB do not only enable the transmission of somatosensory signals to the cerebral cortex (in the sense of a relay station), but are responsible for processing and modulation of incoming information 21, 22, 46. This is reflected in the complex network between VB neurons and cortical as well as other thalamic neurons. This thalamo-cortical network is responsible in part for reciprocal excitatory projections between neurons of the VB and the somatosensory cortex as well as their collateral projections to the GABAergic neurons of the thalamic reticular nucleus (TRN), which, in turn, exerts feedback inhibition onto VB neurons 21, 42. This provides a feedback pathway for modulation and filtering of ascending sensory information which is a general feature of the thalamic stage within sensory systems. The cerebral cortex thus receives information that is strongly filtered and modulated, for example according to the stimulation situation of the sense organs, the degree of attention, or the sleep–wake situation 1, 22, 30, 33, 40, 41, 42, 46.
General anesthetics may interact with the same neuronal networks at the thalamic level, apart from their direct actions on cortical mechanisms of perception and consciousness, and thus may effect a suppression of information about stimuli of the external (and internal) environment normally transmitted to the cortex. Although anesthetics may interact with all stages of the afferent pathway, the thalamus as the input stage to the cortex is a strategic location which may specifically modulate anesthetic action. Recently, the view that anesthetics may exert differential effects on neuronal activity in distinct regions has been put forward 2, 3, 7, 24, 27, 28, 44, 51 and potential influences of anesthetics at the thalamic level have been suggested 2, 3, 4, 5, 11, 16, 31, 36, 45, 46, 47. However, knowledge about the effects of anesthetics on responses of single thalamic neurons elicited by natural stimuli is limited, though suppression of tactile perception is usually observed under general anesthesia during surgery.
The present study investigates the effects of varied concentrations of isoflurane on thalamic mechanosensitive neurons as input to the cerebral cortex in the rat. Keeping in mind, that any effects noted on thalamic neurons may have resulted from actions at one or several sites along the ascending pathway, a comparison was made of responses from thalamo-cortical relay neurons (TCNs) and their specific afferent inputs, trigemino-thalamic fibers (TTFs). It was sought, thereby, to gain an insight into possible differential effects of isoflurane on thalamo-petal second (TTFs) and thalamo-fugal third order neurons (TCNs).
Section snippets
Surgical preparation
The study was performed after the approval of the Hamburg University Animal Research Committee. Anesthesia was induced by intraperitoneal injection of ketamine hydrochloride (100 mg kg−1) in 15 adult Wistar rats (250–340 g body weight). The recording session was started at least 3 h after the administration of ketamine. Thus, it is unlikely that any residual effects of the short acting induction agent were still present (see also below). The trachea was cannulated and the lungs were
Thalamo-cortical relay neurons
A total of 28 TCNs responding to sinus hair or fur stimulation were analysed. All TCNs were located within and distributed throughout the extent of VPM. The location of two of the TCN neurons is shown in Fig. 1B. Under baseline conditions (0.6% isoflurane), 18 (64%) of these neurons were classified as phasically and 10 (36%) as tonically responding. Increasing isoflurane concentrations suppressed ongoing and response activities in a dose-dependent manner in all TCNs studied. The functional
Discussion
The present study shows that isoflurane attenuates ongoing as well as stimulus-evoked neuronal activity in the rat's somatosensory thalamus in a dose-dependent manner. Increasing isoflurane concentrations reduced ongoing activity of low-threshold mechanosensitive TCNs and TTFs to the same extent. The response activities of thalamic input (TTFs) and output neurons (TCNs), however, were affected differently. While a substantial decrease in discharge rate (≥30%) occurred in TTFs only when
Acknowledgements
We would like to thank Ms. Maren Kurschat for expert technical assistance.
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