, 2009; Ma et al., 2010; Kerlin Ibrutinib clinical trial et al., 2010; Hofer et al., 2011; Atallah et al., 2012; but see also

Runyan et al., 2010). Optogenetic perturbations of PV neurons suggest that they may act primarily as gain control in primary visual cortex, strongly affecting the spike rate of excitatory neurons with a smaller effect on the tuning properties (Atallah et al., 2012; Lee et al., 2012), although significant enhancement of orientation tuning of excitatory neurons was reported during optogenetic stimulation of PV neurons (Wilson et al., 2012). SST neurons responded several fold weaker with a delay compared to PV neurons in response to visual stimuli, but, interestingly, SST neurons had a similar orientation tuning selectivity to excitatory neurons and were much more orientation selective than PV neurons (Ma et al., 2010). Recently, SST neurons were found to summate visual inputs from a very large visual field, suggesting that they may mediate surround suppression in mouse primary visual cortex (Adesnik et al., 2012). Although, there is much further work to be done to clarify the computational roles of different types of inhibitory neurons, it is clear that different classes of GABAergic neurons in visual cortex have very different response properties, similar to the findings in mouse barrel cortex. In the future,

it will probably be important to further subdivide the types of GABAergic neurons and it Obeticholic Acid mw will also be essential to begin to subdivide different types of excitatory neurons, perhaps based on their long-range projection targets or through genetic labeling. The sparse AP firing in excitatory neurons contrasts strongly with the high firing rates observed in Ergoloid many inhibitory neurons. This leads to the obvious suggestion that the GABAergic neurons might be responsible for suppressing the activity of excitatory

neurons. Consistent with this idea, local infusion of GABAA-receptor antagonists into L2/3 mouse barrel cortex increases spontaneous AP firing rates in nearby excitatory neurons (Gentet et al., 2010) (Figure 4A). Similarly, optogenetic inhibition of L2/3 PV or SST neurons in vivo also increased the firing rate of L2/3 pyramidal cells (Gentet et al., 2012; Atallah et al., 2012; Adesnik et al., 2012). PV, 5HT3AR, and excitatory neurons have correlated membrane potential fluctuations, so that the inhibitory PV and 5HT3AR neurons fire APs when the excitatory neurons are also most depolarized (Gentet et al., 2010). Excitatory and inhibitory conductances are therefore overall tightly correlated (Okun and Lampl, 2008), in general giving rise to closely balanced excitation and inhibition in neocortical neuronal networks. However, it is interesting to note that SST GABAergic neurons in L2/3 barrel cortex of awake mice have membrane potential fluctuations and firing probabilities that are anticorrelated with all the other nearby cell types (Gentet et al., 2012).