, 2011) or PV neurons (PV-ires-Cre driver mice;

Hippenmeyer et al., 2005), resulted in selective expression of ChR2-EYFP (ChR2+) in the two classes of neurons ( Figures 4A–4C). Afatinib cell line Because CCK or its preprohormone is expressed at low levels in a small fraction of hippocampal PNs ( Taniguchi et al., 2011), we used stereotactic injections of virus localized to CA1 to prevent photoactivation of excitatory projections to CA1. Pulses of 470 nm light generated large excitatory whole-cell photocurrents in infected PV or CCK INs ( Figures 4D2 and 4D3). In cell-attached recordings from ChR2+ INs, a brief train of light pulses at 10 Hz reliably elicited a train of time-locked extracellular currents that reflect reliable spiking. To examine the inhibitory influence of the CCK and PV INs, we recorded light-evoked IPSCs under CP-868596 ic50 voltage-clamp conditions (Vm +10 mV)

from uninfected CA1 PNs (Figure 4D1). Activation of either ChR2+ PV or CCK INs with a single brief (1–2 ms) light pulse focused on the CA1 PN soma layer (Figure S3A) generated large, rapid IPSCs in the PNs (Figures 4E1–4F2). Importantly, the light-evoked IPSCs in the CCK-Cre mice showed little or no change upon application of GluR antagonists, confirming that the IPSCs were caused by direct activation of the CCK INs, rather than disynaptic excitation of INs by ChR2-expressing CCK+ PNs ( Figure S3B). Photoactivation of ChR2+ CCK INs (Figure 4E1) evoked IPSCs in the CA1 PN that were 140% larger than those elicited by photoactivation of ChR2+ PV INs (Figures 4F1, 4F2, and 4G; CCK-Cre mice: 1.584 ± 0.1 nA, n = 25; PV-Cre mice: 0.661 ± 0.05 nA, n = 23; p < 0.0001, CCK versus PV, unpaired t test), a difference maintained across a range of light intensities (p < 0.0001, ANOVA with Tukey’s multiple comparisons test, n = 8; Figures 4E1–4F2 and 4H). The IPSCs mediated by PV INs had more rapid kinetics, with a shorter rise time and half-width, compared to CCK INs. Focal delivery of light over the PN soma at low light intensities (2%–3%) elicited small (50–80 pA) miniature IPSC-like events with

a 50% Levetiracetam failure rate. Consistent with previous paired recordings data (Glickfeld and Scanziani, 2006), the response latency of light-evoked low-amplitude IPSCs was greater for CCK INs (7.58 ± 0.37 ms, n = 8) compared to the PV INs (3.68 ± 0.13 ms, n = 8; p < 0.0001, CCK versus PV, unpaired t test; Figures 4E1–4F2 and H). Next, we assessed whether the induction of ITDP modulates the light-evoked IPSCs. With ChR2 expressed in the CCK INs, the ITDP pairing protocol produced a reliable ∼50% decrease in the light-evoked IPSC in CA1 PNs. The IPSC evoked by a 25% maximal light intensity pulse decreased from 1.24 ± 0.19 nA before ITDP to 0.67 ± 0.21 nA after ITDP (mean ± SEM; p < 0.05, paired t test, n = 5; Figures 5A1–5C). In contrast, when ChR2 was expressed in PV INs, the IPSC evoked by identical photostimulation was unchanged with ITDP (0.69 ± 0.25 nA before versus 0.66 ± 0.