For example, in the rodent somatosensory system, high-frequency inputs occurring during active whisking lead to reduced responsiveness in cortical HCS assay pyramidal neurons due to dynamic network properties such as short-term depression at the thalamocortical synapse and changes in the driving force of excitatory versus inhibitory inputs (Chung et al., 2002 and Crochet et al., 2011). Frequency-dependent effects on olfactory network dynamics have primarily been studied in the OB (Figure 5), although olfactory processing in the PC likely also depends on sniff frequency. Predicted effects of sniff frequency

on OB processing arise from experiments in anesthetized animals or slice preparations in which sniff frequency is mimicked with pulsed electrical stimulation or direct current injection (Balu et al., 2004, Hayar et al., 2004b and Margrie and Schaefer, 2003). These studies have led to predictions that increasing sniff frequency LEE011 in vitro will have distinct, cell type-specific effects on the strength of odorant-evoked activity and the coherence of activity across a population of neurons within the OB. For example, granule cells—GABAergic interneurons thought to mediate

feedback and lateral inhibition of MT cells—show increased synchrony and stronger inhibition onto MT cells at synaptic input frequencies corresponding to active sniffing (Young and Wilson, 1999 and Schoppa, 2006a). In addition, MT cells themselves show increased spike output and temporal precision as input frequency increases into the range of active sniffing oxyclozanide (Balu et al., 2004; Figure 5C). Another important element mediating sniff frequency-dependent changes in OB processing is the external

tufted (ET) cell—an excitatory interneuron in the glomerular-layer. ET cells can drive direct feed-forward excitation as well as indirect (disynaptic) feed-forward inhibition of MT cells and are thus potent regulators of MT excitability (Hayar et al., 2004a and Najac et al., 2011). ET cells show spontaneous spike bursts but their bursts become increasingly entrained to rhythmic ORN inputs as input frequency increases (Hayar et al., 2004b), leading to an increase both in their excitation of MT cells and their activation of inhibitory periglomerular interneurons (PG cells) (Hayar et al., 2004a). In vivo, this effect is predicted to generate an increasingly sharp time-window over which MT cells integrate ORN inputs and may also increase the strength of lateral inhibition between glomeruli (Wachowiak and Shipley, 2006). Overall, the consensus prediction from these circuit-level studies is that frequency-dependent effects within the OB network serve to enhance the inhalation-driven temporal patterning of ORN inputs and increase the reliability and temporal precision of MT cell firing relative to inhalation onset (Balu et al., 2004, Schaefer et al., 2006 and Wachowiak and Shipley, 2006).