“Recordings of large
neuronal ensembles and neural stimulation of high spatial and temporal precision are important requisites for studying the real-time dynamics of neural networks. Multiple-shank silicon probes enable large-scale monitoring of individual Selleckchem Small molecule library neurons. Optical stimulation of genetically targeted neurons expressing light-sensitive channels or other fast (milliseconds) actuators offers the means for controlled perturbation of local circuits. Here we describe a method to equip the shanks of silicon probes with micron-scale light guides for allowing the simultaneous use of the two approaches. We then show illustrative examples of how these compact hybrid electrodes can be used in probing local circuits in behaving rats and mice. A key advantage of these devices is the enhanced spatial precision of stimulation that is achieved by delivering light close to the recording sites of the probe. When paired with the expression of light-sensitive actuators within genetically specified neuronal populations, these devices allow the relatively straightforward and interpretable manipulation of network activity. One of the important challenges in neuroscience is to identify Sotrastaurin cell line the causal links between the collective activity of neurons and behavior. While the study of correlations between ensemble neuronal activity and behavior has produced unprecedented progress in the past decade (Buzsaki et al., 1992;
Wilson & McNaughton, 1993; Harris et al., 2003; Gelbard-Sagiv et al., 2008; Yamamoto & Wilson, 2008; Battaglia et al., 2009; Rizk et al., 2009), the correlational Sclareol nature of these measurements leaves ambiguous the cause-and-effect relationship. A more thorough understanding requires at least two additional steps. The first one is the identification of the multiple neuronal cell types that uniquely contribute to the assembly behavior, rather like members of an orchestra. There are at least two dozen
excitatory and inhibitory neuron types in the cortex, with diverse targets, inputs and uniquely tuned biophysical properties, and existing methods have serious limitations for identifying and segregating these neuron types (Freund & Buzsaki, 1996; Klausberger et al., 2003; Markram et al., 2004; Klausberger & Somogyi, 2008). The second step is a principled manipulation of the spiking activity of these identified cell groups. The recently developed molecular optogenetic tools provide a means to achieve each of the above experimental goals (Deisseroth et al., 2006; Zhang et al., 2007a; O’ Connor et al., 2009). Optical stimulation of genetically targeted neurons expressing light-sensitive channelrhodopsin-2 (Chr2 has recently been reported to be a rapid activator of neuronal firing with potential cell-type selectivity (Nagel et al., 2003; Boyden et al., 2005; Li et al., 2005; Ishizuka et al., 2006; Han & Boyden, 2007; Zhang et al., 2007b).