Electrophysiological Classification of Somatostatin-Positive Interneurons in Mouse Sensorimotor Cortex
Journal of Neurophysiology
Prince. Electrophysiological classification of somatostatin-positive interneurons in mouse sensorimotor cortex. fication of inhibitory interneurons is critical in determining their role in normal information processing and pathophysiological conditions such as epilepsy. Classification schemes have relied on morphological, physiological, biochemical, and molecular criteria; and clear correlations have been demonstrated between firing patterns and cellular markers such as neuropeptides and
... peptides and calcium-binding proteins. This molecular diversity has allowed generation of transgenic mouse strains in which GFP expression is linked to the expression of one of these markers and presumably a single subtype of neuron. In the GIN mouse (EGFP-expressing Inhibitory Neurons), a subpopulation of somatostatin-containing interneurons in the hippocampus and neocortex is labeled with enhanced green fluorescent protein (EGFP). To optimize the use of the GIN mouse, it is critical to know whether the population of somatostatin-EGFP-expressing interneurons is homogeneous. We performed unsupervised cluster analysis on 46 EGFP-expressing interneurons, based on data obtained from whole cell patch-clamp recordings. Cells were classified according to a number of electrophysiological variables related to spontaneous excitatory postsynaptic currents (sEPSCs), firing behavior, and intrinsic membrane properties. EGFP-expressing interneurons were heterogeneous and at least four subgroups could be distinguished. In addition, multiple discriminant analysis was applied to data collected during whole cell recordings to develop an algorithm for predicting the group membership of newly encountered EGFP-expressing interneurons. Our data are consistent with a heterogeneous population of neurons based on electrophysiological properties and indicate that EGFP expression in the GIN mouse is not restricted to a single class of somatostatin-positive interneuron. composition, kinetic, and permeation properties of AMPA receptors in single neocortical nonpyramidal cells. J Neurosci 17: 6685-6696, 1997. Bacci A, Huguenard JR, and Prince DA. Functional autaptic neurotransmission in fast-spiking interneurons: a novel form of feedback inhibition in the neocortex. J Neurosci 23: 859 -866, 2003. Bacci A, Rudolph U, Huguenard JR, and Prince DA. Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclasses. J Neurosci 23: 9664 -9674, 2003. Bartos M, Vida I, Frotscher M, Geiger JR, and Jonas P. Rapid signaling at inhibitory synapses in a dentate gyrus interneuron network. J Neurosci 21: 2687-2698, 2001. Bond CT, Maylie J, and Adelman JP. Small-conductance calcium-activated potassium channels. Ann NY Acad Sci 868: 370 -378, 1999. Buckmaster PS and Dudek FE. Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. J Comp Neurol 385: 385-404, 1997. Buckmaster PS and Jongen-Relo AL. Highly specific neuron loss preserves lateral inhibitory circuits in the dentate gyrus of kainate-induced epileptic rats. J Neurosci 19: 9519 -9529, 1999. Cathala L, Holderith NB, Nusser Z, DiGregorio DA, and Cull-Candy SG. Changes in synaptic structure underlie the developmental speeding of AMPA receptor-mediated EPSCs. Nat Neurosci 8: 1310 -1318, 2005. Cauli B, Audinat E, Lambolez B, Angulo MC, Ropert N, Tsuzuki K, Hestrin S, and Rossier J. Molecular and physiological diversity of cortical nonpyramidal cells. Classification of fusiform neocortical interneurons based on unsupervised clustering. Proc Natl Acad Sci USA 97: 6144 -6149, 2000. Chow A, Erisir A, Farb C, Nadal MS, Ozaita A, Lau D, Welker E, and Rudy B. K(ϩ) channel expression distinguishes subpopulations of parvalbumin-and somatostatin-containing neocortical interneurons. J Neurosci 19: 9332-9345, 1999. Davies P, Katzman R, and Terry RD. Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementa. Nature 288: 279 -280, 1980. DeFelipe J. Neocortical neuronal diversity: chemical heterogeneity revealed by colocalization studies of classic neurotransmitters, neuropeptides, calciumbinding proteins, and cell surface molecules. Cereb Cortex 3: 273-289, 1993. DeFelipe J. Types of neurons, synaptic connections and chemical characteristics of cells immunoreactive for calbindin-D28K, parvalbumin and calretinin in the neocortex. DeFelipe J and Farinas I. The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. Prog Neurobiol 39: 563-607, 1992. DeFelipe J, Gonzalez-Albo MC, Del Rio MR, and Elston GN. Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey. J Comp Neurol 412: 515-526, 1999. DeFelipe J, Hendry SH, Hashikawa T, Molinari M, and Jones EG. A microcolumnar structure of monkey cerebral cortex revealed by immunocytochemical studies of double bouquet cell axons. Neuroscience 37: 655-673, 1990. de Lima AD and Morrison JH. Ultrastructural analysis of somatostatinimmunoreactive neurons and synapses in the temporal and occipital cortex of the macaque monkey. J Comp Neurol 283: 212-227, 1989. Deuchars J and Thomson AM. Innervation of burst firing spiny interneurons by pyramidal cells in deep layers of rat somatomotor cortex: paired intracellular recordings with biocytin filling. Neuroscience 69: 739 -755, 1995. Elston GN and Gonzalez-Albo MC. Parvalbumin-, calbindin-, and calretininimmunoreactive neurons in the prefrontal cortex of the owl monkey (Aotus trivirgatus): a standardized quantitative comparison with sensory and motor areas. Brain Behav Evol 62: 19 -30, 2003. Erisir A, Lau D, Rudy B, and Leonard CS. Function of specific K(ϩ) channels in sustained high-frequency firing of fast-spiking neocortical interneurons.