The research described in this application is designed to expound upon the recent discoveries of state-dependent suppression of sensory transmission through the trigeminal sensory nuclear complex and trigemino-thalamic tract. The investigators will explore the pharmacological basis for presynaptic and postsynaptic inhibition of sensory transmission through the trigeminal sensory nuclear complex and trigemino-thalamic tract, which occurs during active sleep. They will utilize the unique approach of examining active sleep-related presynaptic gating mechanisms not only at the level of primary afferents, but also at the terminal arbors of the second order sensory tract cells located in the contralateral thalamus. Specifically, extracellular recording techniques, in conjunction with procedures for assessing terminal excitability prior to, during, and following microinotophoresis of bicuculline in the normally respiring cat will be utilized to investigate whether active sleep-related depolarization of tooth pulp afferents, and trigemino-thalamic tract afferents is mediated by classical GABAA receptors. A series of computer controlled procedures for assessing the antidromic firing index of extracellularly recorded trigemino-thalamic tract neurons will also be performed on data obtained prior to, during, and following recovery from microinotophoresis of strychnine and bicuculline. These studies are designed to investigate whether active sleep-related postsynaptic inhibition of sensory transmission through the trigemino-thalamic tract is mediated by glycine and/or GABA receptors. Additionally, the state-specific differential gate control of primary afferent input to trigemino-thalamic tract and other trigeminal sensory nuclear complex neurons via large vs. small diameter fibers, which was recently proposed, will be further tested by comparing the extracellularly recorded responses of these cells to natural forms of stimuli (air puff, cooling, warming) applied to orofacial receptive fields during different levels of vigilance. The proposed studies will provide, in the chronic unanesthetized cat, a comprehensive description and quantitative analysis of active sleep-related control mechanisms influencing individual trigemino-thalamic tract and other trigeminal sensory nuclear complex neurons. The studies proposed should provide not only important new insights into normal functioning of trigemino-thalamic tract and other trigeminal sensory nuclear complex neurons as a function of behavioral state but also provide a data base complimentary to that which already exists for active sleep state-dependent suppression of somatomotor outflow. Such data are essential if further insights regarding the fundamental nature of sleep, and how the sleep states affect ascending sensory transmission in distinct sensory channels are to be realized. The new insights will contribute toward understanding sleep disorders, e.g., REM-related paraesthesias and Behavioral Disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS032306-04
Application #
2631888
Study Section
Special Emphasis Panel (ZRG2-BPO (01))
Program Officer
Kitt, Cheryl A
Project Start
1994-08-01
Project End
2001-05-31
Budget Start
1998-07-01
Budget End
1999-05-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of British Columbia
Department
Type
DUNS #
800772162
City
Vancouver
State
BC
Country
Canada
Zip Code
V6 1-Z3
Taepavarapruk, N; Taepavarapruk, P; John, J et al. (2008) State-dependent changes in glutamate, glycine, GABA, and dopamine levels in cat lumbar spinal cord. J Neurophysiol 100:598-608
Kohlmeier, Kristi A; Soja, Peter J; Kristensen, Morten P (2006) Disparate cholinergic currents in rat principal trigeminal sensory nucleus neurons mediated by M1 and M2 receptors: a possible mechanism for selective gating of afferent sensory neurotransmission. Eur J Neurosci 23:3245-58
Taepavarapruk, Niwat; McErlane, Shelly A; Chan, Angela et al. (2004) State-dependent GABAergic inhibition of sciatic nerve-evoked responses of dorsal spinocerebellar tract neurons. J Neurophysiol 92:1479-90
Cairns, Brian E; Kiang, Tony; McErlane, Shelly A et al. (2003) Eye movement-related modulation of trigeminal neuron activity during active sleep and wakefulness. Brain Res 975:110-9
Taepavarapruk, Niwat; McErlane, Shelly A; Soja, Peter J (2002) State-related inhibition by GABA and glycine of transmission in Clarke's column. J Neurosci 22:5777-88
Soja, Peter J; Taepavarapruk, Niwat; Pang, Walton et al. (2002) Transmission through the dorsal spinocerebellar and spinoreticular tracts: wakefulness versus thiopental anesthesia. Anesthesiology 97:1178-88
Soja, P J; Pang, W; Taepavarapruk, N et al. (2001) On the reduction of spontaneous and glutamate-driven spinocerebellar and spinoreticular tract neuronal activity during active sleep. Neuroscience 104:199-206
Cairns, B E; McErlane, S A; Fragoso, M C et al. (1999) Tooth pulp- and facial hair mechanoreceptor-evoked responses of trigeminal sensory neurons are attenuated during ketamine anesthesia. Anesthesiology 91:1025-35
Cairns, B E; Soja, P J (1998) Active sleep-related depolarization of feline trigemino-thalamic afferent terminals. Neuroreport 9:565-70
Cairns, B E; McErlane, S A; Fragoso, M C et al. (1996) Spontaneous discharge and peripherally evoked orofacial responses of trigemino-thalamic tract neurons during wakefulness and sleep. J Neurosci 16:8149-59