GABAA Receptor in the Thalamic Specific Relay System Contributes to the Propofol-Induced Somatosensory Cortical Suppression in Rat

Interaction with the gamma-aminobutyric-acid-type-A (GABAA) receptors is recognized as an important component of the mechanism of propofol, a sedative-hypnotic drug commonly used as anesthetic. However the contribution of GABAA receptors to the central nervous system suppression is still not well understood, especially in the thalamocortical network. In the present study, we investigated if intracerebral injection of bicuculline (a GABAA receptor antagonist) into the thalamus ventral posteromedial nucleus (VPM, a thalamus specific relay nuclei that innervated S1 mostly) could reverse propofol-induced cortical suppression, through recording the changes of both spontaneous and somatosensory neural activities in rat’s somatosensory cortex (S1). We found that after injection of bicuculline into VPM, significant increase of neural activities were observed in all bands of local field potentials (total band, 182±6%), while the amplitude of all components in somatosensory evoked potentials were also increased (negative, 121±9% and positive, 124±6%).These data support that the potentiation of GABAA receptor-mediated synaptic inhibition in a thalamic specific relay system seems to play a crucial role in propofol-induced cortical suppression in the somatosensory cortex of rats.

[1]  S. Ikemoto Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex , 2007, Brain Research Reviews.

[2]  Olivier Pourquié,et al.  Segmental patterning of the vertebrate embryonic axis , 2008, Nature Reviews Genetics.

[3]  C. Koch,et al.  The Neural Correlates of Consciousness , 2008, Annals of the New York Academy of Sciences.

[4]  R W Guillery,et al.  The role of the thalamus in the flow of information to the cortex. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[5]  John R. Huguenard,et al.  Thalamic synchrony and dynamic regulation of global forebrain oscillations , 2007, Trends in Neurosciences.

[6]  Valérie Campagna-Slater,et al.  Anaesthetic binding sites for etomidate and propofol on a GABAA receptor model , 2007, Neuroscience Letters.

[7]  M. Heinricher,et al.  GABA-mediated inhibition in rostral ventromedial medulla: role in nociceptive modulation in the lightly anesthetized rat , 1991, Pain.

[8]  Nathan S White,et al.  Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness , 2003, NeuroImage.

[9]  F. Ebner,et al.  The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons. , 1994, Journal of neurophysiology.

[10]  R. Zatorre,et al.  Cortical Processing of Complex Auditory Stimuli during Alterations of Consciousness with the General Anesthetic Propofol , 2006, Anesthesiology.

[11]  M. Boly,et al.  Breakdown of within- and between-network Resting State Functional Magnetic Resonance Imaging Connectivity during Propofol-induced Loss of Consciousness , 2010, Anesthesiology.

[12]  Tian Yu,et al.  Altered Thalamocortical Functional Connectivity by Propofol Anesthesia in Rats , 2011, Pharmacology.

[13]  M. Funahashi,et al.  Suppression of the hyperpolarization-activated inward current contributes to the inhibitory actions of propofol on rat CA1 and CA3 pyramidal neurons , 2003, Neuroscience Research.

[14]  D. Bayliss,et al.  Suppression of ih contributes to propofol-induced inhibition of mouse cortical pyramidal neurons. , 2005, Journal of neurophysiology.

[15]  B. Connors,et al.  VPM and PoM nuclei of the rat somatosensory thalamus: intrinsic neuronal properties and corticothalamic feedback. , 2007, Cerebral cortex.

[16]  R. Llinás,et al.  Consciousness and the Brain , 2001 .

[17]  R. Llinás,et al.  The neuronal basis for consciousness. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[18]  B. Antkowiak,et al.  Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. , 2006, British journal of anaesthesia.

[19]  G. Edelman Naturalizing consciousness: A theoretical framework , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  E. John The neurophysics of consciousness , 2002, Brain Research Reviews.

[21]  R. Llinás,et al.  Consciousness and the brain. The thalamocortical dialogue in health and disease. , 2001, Annals of the New York Academy of Sciences.

[22]  T Vilis,et al.  Functional MRI activity in the thalamus and occipital cortex of anesthetized dogs induced by monocular and binocular stimulation. , 2001, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[23]  Stephen M. Rao,et al.  Propofol disrupts functional interactions between sensory and high‐order processing of auditory verbal memory , 2012, Human brain mapping.

[24]  N. Franks General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal , 2008, Nature Reviews Neuroscience.

[25]  Michael T Alkire,et al.  Thalamic Microinjection of Nicotine Reverses Sevoflurane-induced Loss of Righting Reflex in the Rat , 2007, Anesthesiology.

[26]  Jeanne T Paz,et al.  Focal Cortical Infarcts Alter Intrinsic Excitability and Synaptic Excitation in the Reticular Thalamic Nucleus , 2010, The Journal of Neuroscience.

[27]  A. Oniz,et al.  Spectral Pattern Analysis of Propofol Induced Spindle Oscillations in the Presence of Auditory Stimulations , 2010, The open neuroimaging journal.

[28]  George A Mashour,et al.  Integrating the Science of Consciousness and Anesthesia , 2006, Anesthesia and analgesia.

[29]  N. Juul,et al.  Regional cerebral blood flow and glucose metabolism during propofol anaesthesia in healthy subjects studied with positron emission tomography , 2012, Acta anaesthesiologica Scandinavica.

[30]  G. Tononi,et al.  Consciousness and Anesthesia , 2008, Science.

[31]  D. Barth,et al.  Topographic analysis of field potentials in rat vibrissa/barrel cortex , 1991, Brain Research.

[32]  A. Namiki,et al.  The Anticonvulsant Action of Propofol on Epileptiform Activity in Rat Hippocampal Slices , 2004, Anesthesia and analgesia.

[33]  Anthony G. Hudetz,et al.  Volatile anesthetics disrupt frontal-posterior recurrent information transfer at gamma frequencies in rat , 2005, Neuroscience Letters.