Fanselow EE, Richardson KA, Connors BW. Selective, statedependent activation of somatostatin-expressing inhibitory interneurons in mouse neocortex. J Neurophysiol 100: 2640 -2652, 2008. First published September 17, 2008 doi:10.1152/jn.90691.2008. The specific functions of subtypes of cortical inhibitory neurons are not well understood. This is due in part to a dearth of information about the behaviors of interneurons under conditions when the surrounding circuit is in an active state. We investigated the firing behavior of a subset of inhibitory interneurons, identified using mice that express green fluorescent protein (GFP) in a subset of somatostatin-expressing inhibitory cells ("GFP-expressing inhibitory neuron" [GIN] cells). The somata of the GIN cells were in layer 2/3 of somatosensory cortex and had dense, layer 1-projecting axons that are characteristic of Martinotti neurons. Interestingly, GIN cells fired similarly during a variety of diverse activating conditions: when bathed in fluids with low-divalent cation concentrations, when stimulated with brief trains of local synaptic inputs, when exposed to group I metabotropic glutamate receptor agonists, or when exposed to muscarinic cholinergic receptor agonists. During these manipulations, GIN cells fired rhythmically and persistently in the theta-frequency range (3-10 Hz). Synchronous firing was often observed and its strength was directly proportional to the magnitude of electrical coupling between GIN cells. These effects were cell type specific: the four manipulations that persistently activated GIN cells rarely caused spiking of regularspiking (RS) pyramidal cells or fast-spiking (FS) inhibitory interneurons. Our results suggest that supragranular GIN interneurons form an electrically coupled network that exerts a coherent 3-to 10-Hz inhibitory influence on its targets. Because GIN cells are more readily activated than RS and FS cells, it is possible that they act as "first responders" when cortical excitatory activity increases.
We experimentally confirmed predictions that modulation of the neuronal threshold with electrical fields can speed up, slow down, and even block traveling waves in neocortical slices. The predictions are based on a Wilson-Cowan-type integro-differential equation model of propagating neocortical activity. Wave propagation could be modified quickly and reversibly within targeted regions of the network. To the best of our knowledge, this is the first example of direct modulation of the threshold to control wave propagation in a neural system.Traveling waves in excitable media are commonly observed in physical [1,2], chemical [3], and biological [4][5][6] systems. Mathematical models have been developed in conjunction with these experimental systems to provide a deeper understanding of the dynamics and infer how individual experimental parameters of the system, such as threshold, contribute to these dynamics [5,[7][8][9][10]. Rapid access to system parameters would offer the means to control pattern formation and dynamics in these systems.Successful modulation of dynamics has been accomplished in chemical, cardiac, and neural systems. In the Belousov-Zhabotinsky chemical reaction system, modulation of excitability through local changes in illumination of a light sensitive catalyst allowed control of wave propagation [11]. Electric fields modulated activity propagation in heart tissue [12]. The propagation speed of excitation waves in neocortex has been slowed by pharmacologically interfering with chemical synaptic transmission [13].It has been previously shown that electric fields can modulate neuronal thresholds by quickly and reversibly polarizing asymmetric neurons [14]. Electric fields as small as 140 μV/mm have been observed to modulate neural firing [15]. Polarization occurs on time scales of about 20 ms and can be maintained for many seconds or minutes [16]. Applied electric fields have been used to adaptively control seizure formation in vitro [17], modulate epileptiform activity in vivo, and dynamically probe activity changes associated with impending seizures [18].We show here that electric fields can quickly alter traveling wave dynamics in ways predicted by theory through direct modulation of neuronal threshold. To our knowledge, this is the first report of control of wave propagation through direct modulation of excitability threshold in any neural system. Wilson and Cowan [19] developed a set of integro-differential equations to form a continuum model of cortex which demonstrated traveling waves. This model was recently modified [20] to represent traveling pulse propagation in disinhibited neocortex [21]. The model predicts that
Gap junctions (GJs) electrically couple GABAergic neurons of the forebrain. The spatial organization of neuron clusters coupled by GJs is an important determinant of network function, yet it is poorly described for nearly all mammalian brain regions. Here we used a novel dye-coupling technique to show that GABAergic neurons in the thalamic reticular nucleus (TRN) of mice and rats form two types of GJ-coupled clusters with distinctive patterns and axonal projections. Most clusters are elongated narrowly along functional modules within the plane of the TRN, with axons that selectively inhibit local groups of relay neurons. However, some coupled clusters have neurons arrayed across the thickness of the TRN and target their axons to both first-and higher-order relay nuclei. Dye coupling was reduced, but not abolished, among cells of connexin36 knock-out mice. Our results suggest that GJs form two distinct types of inhibitory networks that correlate activity either within or across functional modules of the thalamus.
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