GABAA Receptors and the Dynamics of Cortical Inhibitory Circuits
Office Phone: (608) 261-1143, (608) 263-6662
We are interested in how sensory stimuli are represented in the firing patterns of cells in neocortex, and how general anesthetics disrupt this coding process. We use the auditory system of mice and rats as a model system, and we are pursuing these questions using electrophysiological techniques in vitro and electrophysiological and behavioral techniques in vivo.
Regulation of spike timing by GABAergic interneurons in auditory cortex in vitro. We are particularly interested in interneurons that release the inhibitory neurotransmitter GABA and act locally to regulate neural activity. We use patch clamp electrophysiology in mouse auditory thalamocortical slices to determine how GABAA receptor-mediated inhibition shapes the temporal patterns of activity generated in interneurons and pyramidal cells, and the role of modulation of inhibitory postsynaptic currents (IPSCs) by anesthetic agents in altering cortical network activity. An organizing principle of GABAergic cells in neocortex is that they are mutually connected and form interneuronal networks whose activity is often synchronous and thus can produce profound effects on large groups of targeted pyramidal cells. We are exploring how the strength and type of connections within these networks determine the types of stable firing patterns using paired recordings and the dynamic clamp technique. In addition, we are studying large networks by bulk-loading cells in slices with Ca indicator dyes and use confocal microscopy to image Ca transients representing spiking activity in these networks.
Sensory discrimination and electrophysiological recordings in behaving rats. Brain slice experiments allow us to answer detailed questions at the cellular and circuit levels, but to relate these data to the question of stimulus representation in the brain we also need to understand how animals perceive sensory stimuli under normal conditions and when inhibition is modulated by anesthetic agents. We train rats to perform sensory discrimination tasks, record cortical activity evoked during these tasks, and analyze how activity changes with performance. The difficulty of the task is adjusted either by altering stimulus parameters (i.e. making the stimuli more or less similar) and/or by applying anesthetic agents at subhypnotic doses. Recordings of neural activity using chronically-implanted electrodes indicate whether effects on performance are reflected in changes in the similarity of the neural responses to the two stimuli (i.e. if behavioral discrimination degrades, is there an associated decrease in the discriminability of the neural responses?).
- Burlingame, R.H., S. Shrestha, M.R. Rummel, M.I. Banks. 2007. Sub-hypnotic doses of isoflurane impair auditory discrimination in rats. Anesthesiology 106: 754-762.
- Verbny, Y.I., F. Erdélyi, G. Szabó, M.I. Banks. 2006. Properties of a population of GABAergic cells in murine auditory cortex weakly excited by thalamic stimulation. J. Neurophysiology 96: 3194-3208.
- Merriam, E.B., T.I. Netoff, and M.I. Banks. 2005. Bistable network behavior of layer I interneurons in auditory cortex. J. Neurosci. 25: 6175-6186.
- Verbny Y.I., E.B. Merriam, and M.I. Banks. 2005. Modulation of g-aminobutyric acid type A receptor-mediated spontaneous inhibitory postsynaptic currents in auditory cortex by midazolam and isoflurane. Anesthesiology 102: 962-969.
- Perouansky M., M.I. Banks, and R.A. Pearce. 2005. Differential effects of the non-immobilizer 1,2dichlorohexafluorocyclobutane (F6,2N) and isoflurane on extrasynaptic GABAA receptors. Anesthesia and Analgesia 100: 1667-1673.
- Netoff T.I., M.I. Banks, A.D. Dorval, C.D. Acker, J.S. Haas, N. Kopell, and J.A. White. 2005. Synchronization in hybrid neuronal networks of the hippocampal formation. J. Neurophysiol. 93:1197-1208.
- Benkwitz C., M.I. Banks, and R.A. Pearce. 2004. Influence of GABAA receptor γ2 splice variants on receptor kinetics and isoflurane modulation. Anesthesiology 101: 924-936.
- Banks M.I., J.A. Hardie, and R.A. Pearce. 2002. Development of GABAA receptor-mediated inhibitory postsynaptic currents in hippocampus. J. Neurophysiol. 88: 3097-3107.
- White, J.A., M.I. Banks, N. Kopell, and R.A. Pearce. 2000. Networks of interneurons with fast and slow GABAA kinetics provide substrate for mixed gamma-theta rhythm. Proc. Nat. Acad. Sci. 97: 8128-8133.
- Banks, M.I., J.A. White, and R.A. Pearce. 2000. Interactions between distinct GABAA circuits in hippocampus. Neuron 25: 449-457.
- Banks, M.I. and R.A. Pearce. 2000. Kinetic differences between synaptic and extrasynaptic GABAA receptors in CA1 pyramidal cells. J. Neurosci. 20: 937-948.
- Banks, M.I. and R.A. Pearce. 1999. Dual actions of volatile anesthetics on GABAA IPSCs: Dissociation of blocking and prolonging effects. Anesthesiology 90: 120-134.
- Banks, M.I., T-B. Li, and R.A. Pearce. 1998. The synaptic basis of GABAA,slow. J. Neurosci. 18: 1305-1317.