These evoked currents were blocked by NBQX (12.9 ± 4.5% of control, n = 5) but had unusual properties including slow kinetics (10%–90% rise time 6.7 ± 0.9 ms, decay τ 36.3 ± 1.1 ms, n = 19), virtually no trial-to-trial amplitude variability (coefficient of variation 0.05 ± 0.01, n = 19), and little sensitivity to membrane potential (7.5 ± 2.7% reduction in amplitude from −80 mV to −40 mV, n = 7) (Figure S1 available

online). These responses were also observed in cells in which the primary apical dendrite was severed (n = 3). Although we cannot rule out the possibility that these Selleckchem Navitoclax small responses reflect synaptic contacts that only occur onto electrotonically remote regions of lateral dendrites or axons, they could also reflect glutamate spillover from cortical fibers onto distal processes, intracellular detection of local field potentials, or gap junctional coupling with cells receiving

direct synaptic input. Regardless of their exact origin, these small currents did not have an obvious effect on mitral cell excitability since they caused only weak membrane depolarization (0.3 ± 0.1 mV at rest, n = 9) and never elicited APs. Granule cells are thought to be the major target of direct excitation from cortical feedback projections (Strowbridge, 2009). Indeed, brief light GSK1120212 ic50 flashes evoked EPSCs in GCs (Figure 3A1) with fast kinetics (10%–90% rise time: 0.76 ± 0.06 ms, decay τ: 1.49 ± 0.08 ms, amplitude range:13 to 587 pA, n = 20) and little jitter in their onset times (SD = 0.23 ± 0.02 ms, n = 20). Light-evoked EPSCs in GCs were abolished by tetrodotoxin (TTX, 1 μM, n = 6) but were partially recovered following subsequent application of the K+ channel blocker 4-aminopyridine (4-AP, MTMR9 1 mM, n = 5; Figure 3A2). Consistent with previous studies (Petreanu et al., 2009), the synaptic response elicited in the presence of TTX and 4-AP indicates that we could trigger transmission via direct ChR2-mediated depolarization of boutons, however, the responses we observe under normal conditions reflect AP-mediated transmitter release from cortical fibers. Membrane depolarization (Vm = +40 mV)

in the presence of picrotoxin (100 μM) revealed a slow NMDAR component to cortically-driven EPSCs that was abolished by APV (n = 4), while the fast EPSCs were blocked by NBQX (n = 7, Figure 3A3). The current-voltage relationship of the isolated AMPAR response was linear (n = 5; Figure 3A4), indicating that AMPARs at cortical synapses on GCs are Ca2+-impermeable (Hollmann and Heinemann, 1994). We think it likely that GCs are a major source of cortically-evoked disynaptic inhibition onto mitral cells. Cell-attached recordings of GCs revealed that cortical input is sufficient to drive GCs to spike threshold (n = 5; Figure 3B1). Furthermore, simultaneous whole-cell recordings indicated that the onset of evoked mitral cell IPSCs followed EPSCs in GCs with a disynaptic latency (3.2 ± 0.4 ms, n = 7; Figure 3B2).