These inputs are strongly sniff-modulated but the time course of inputs within a glomerulus is thought to be homogeneous (Wachowiak et al., 2004). Thus, the phase difference between MCs and TCs is likely to be generated by either OB circuitry or differential inputs from other brain areas. To assess the potential role of inhibitory interneurons, we performed whole-cell recordings while

pharmacologically blocking fast GABAergic transmission (Figure 4A). In order to avoid the epileptic discharges that are common with applications of GABAergic antagonists alone in vivo (Figures S4A–S4D), we applied a titrated mixture of a GABAA antagonist, gabazine (0.4 mM), and a potent GABAA agonist, muscimol (2 mM). The high effective dose of exogenous drugs should outcompete endogenous GABA for action on GABAA receptors (Bao et al., 2002), consequently clamping GABAA-mediated inhibition without substantially altering network excitability. selleck kinase inhibitor This requires that the blockade of GABAA receptors by gabazine is on average closely counterbalanced by muscimol-mediated, stimulus-independent opening of synaptic and extrasynaptic GABAA receptors. Consistent with this, the “GABAA-clamp” resulted in comparable

average baseline firing rates as well as input resistance, and subthreshold oscillatory activity was efficiently maintained (Figures 4B–4D). Notably, synaptic inhibition, as measured by evoking recurrent inhibition in vivo (Abraham et al., 2010), was indeed robustly and significantly reduced (1,186mV ± 82mV Oxygenase × ms control versus 741mV ± 109mV × ms, p = 0.004, 11 cells; Figure 4E). Thus, GABAA-clamp Selleckchem Icotinib through combined application of gabazine and muscimol leaves basic network stability seemingly unperturbed

while clamping the inhibitory circuitry. As a consequence of GABAA-clamp the phase of virtually all MCps shifted to the control TC phase (ΦVm = 5.74 + [−0.50 0.36] radians, control, versus 2.06 + [−0.59 0.65], GABAA-clamp, p = 0.016, n = 7 cells, circular two sample test, Figures 4F and 4G). The phase of TCps on the other hand was completely unaffected (Figures 4H and 4I). Similarly, preferred AP firing phase for MCps shifted to the TC phase under GABAA-clamp (Figures S4E and S4F). This strongly suggests that the phase difference between TCs and MCs is set up by inhibitory networks in the OB, that have the effect of shifting the MC phase away from the TC phase. This robustness of TC and sensitivity of MC phase in response to network perturbation provokes the question how sensory input might differentially affect the two principal neurons. For high odor concentrations (5%–10% of saturated vapor) MCs and TCs frequently respond to odor stimulation with a significant increase in firing rate (27 of 174 cell-odor pairs are purely excitatory; Figures 5A–5C). As observed under GABAA-clamp, average MCp phase was again drastically shifted (from 5.