During the former, the depolarizing phase, neurons become increasingly sensitive to excitatory input and emit spikes. During the following hyperpolarizing phase, they are exposed to massive

inhibition by synchronously bursting inhibitory interneurons, emit no spikes, and are little susceptible to excitatory LY2157299 inputs (Wang and Buzsáki, 1996; Whittington et al., 1995). Thus, by adjusting oscillation frequency and phase of anatomically connected cell clusters, effective coupling between these clusters can be enhanced by assuring that the respective excitatory inputs are synchronized and arrive at the peak of susceptibility while coupling can be virtually abolished if phase relations among the oscillating clusters are such that excitatory volleys arrive during the phase of low susceptibility (Fries, 2005; Womelsdorf et al., 2007). Experimental and theoretical evidence indicates that the networks of mutually interacting GABAergic interneurons are crucially check details involved as pacemakers in the generation of high-frequency oscillations in local circuits (Traub et al., 2004;

Wang and Buzsáki, 1996). GABAergic interneurons, especially those expressing the calcium binding protein parvalbumin (PV), play a particularly important role in the generation of high-frequency oscillations because of their fast-spiking characteristics and the short time constants of synaptic interactions mediated by these cells (Bartos et al., 2007). In a landmark paper, Sohal Etomidate and colleagues (2009) probed the influence of up- and downregulation of PV interneurons on gamma-band oscillations in mice. Inhibition of PV interneurons led to an immediate suppression of 30–80 Hz oscillations while 10–30 Hz oscillations increased in power. In contrast, increasing PV-interneuron-mediated feedback inhibition by boosting principal cell activity enhanced gamma-band power (Cardin et al., 2009). Recent studies have also examined the specific

role of glutamatergic inputs to PV interneurons for the generation of coordinated network activity. Carlén et al. (2012) examined the effect of deleting NMDA NR1 receptors on PV interneurons applying an optogenetic approach. Mice with a reduced expression of NR1 subunits were characterized by increased spontaneous 36–44 Hz activity in somatosensory cortex compared to control animals while showing reduced gamma-band activity during sensory stimulation which was accompanied by dysfunctions in habituation, working memory, and associative learning. Optic stimulation of PV interneurons revealed diminished spike synchronization as well as increased spike latency and variance in spike timing. Similarly, Belforte et al. (2010) showed that NR1 deletion in GABAergic interneurons resulted in increased firing of pyramidal cells and reduced synchronization of neuronal responses in slices, suggesting that NMDA-receptor hypofunctioning is associated with impaired temporal coordination of neuronal activity.