GABAergic inhibition is mediated by a diverse range of interneuron populations, with distinct anatomical, physiological and biochemical properties which are likely to correlate with specific network functions. We compared the properties of synaptic inhibition at somatic/proximal dendritic synapses formed by fast-spiking (FS) basket cells, with transmission at dendritic synapses formed by non-fast-spiking (NFS), hilar commisural-associational path-related (HICAP) cells on granule cells of the dentate gyrus. In additional experiments we used a dynamic current clamp circuit to inject naturalistic synaptic conductances into interneurons and thus compare their responses to simulated population activity.
Transverse hippocampal slices were prepared from 12- to 20-day-old rats, humanely killed in accordance with the Institutional Animal Care and Use Committee. Dual whole-cell patch clamp recordings were made from interneurons, current-clamped at -60 mV, and granule cells, voltage-clamped at -60 mV. Patch pipettes were filled with 0.1 % biocytin and all interneurons were subsequently identified anatomically. Data are means ± S.E.M. Statistical significance was evaluated using Student’s unpaired t test (P < 0.05).
FS and NFS interneurons had similar resting potentials (-58 ± 1 and -55 ± 1 mV, n = 27 FS and 34 NFS) but significantly different input resistances (105 ± 6 vs. 202 ± 16 MV, P < 0.05) and membrane time constants (33 ± 3 vs. 49 ± 2 ms, P < 0.05). In response to depolarising current steps (1 nA, 1 s) FS cells fired more spikes than NFS cells (72 ± 5 vs. 14 ± 3, P < 0.05) with a greater maximum spike rate (81 ± 4 vs. 65 ± 4 Hz, P < 0.05). Granule cell IPSCs evoked by both interneuron populations had similar amplitudes (99 ± 21 pA for FS, n = 27, 70 ± 15 pA for NFS, n = 34) and decay kinetics (t{special} = 22 ± 0.8 ms for FS, 24 ± 1 ms for NFS); however, dendritic NFS IPSCs had slower rise times and synaptic latencies. Paired-pulse depression was greater for NFS (21 ± 0.03 %) than FS IPSCs (16 ± 0.02 %, P < 0.05) and IPSCs evoked at 10 and 50 Hz were reliable but strongly depressing for FS synapses, whereas NFS IPSC trains did not show depression. Injection of simulated synaptic conductances, based on synaptic events recorded experimentally, revealed that FS interneurons fired at lower frequencies and with greater precision than NFS cells.
These data indicate that presynaptic physiological properties distinguish somatic and dendritic inhibition and suggest that FS and NFS cells respond differently during network activity.
This work was supported by The Epilepsy Foundation.