Abstracts

RATIONALE: The excitability of granule cells (GC) in dentate gyrus is regulated by diverse GABAergic interneurons that can be divided into two groups, either anatomically (somatic versus dendritic innervation of GCs) or physiologically (fast-spiking (FS) versus non-fast-spiking (NFS)). Our objective was to examine the anatomy, spiking properties and synaptic physiology of these interneurons, in order to better understand their different roles in hippocampal network dynamics.
METHODS: Paired whole-cell patch clamp recordings were made from synaptically coupled interneurons and granule cells, in hippocampal slices from 12-20 day old rats, using standard solutions, at room temperature. Biocytin was included in the pipette solutions for subsequent anatomical characterization. Spikes evoked in the presynaptic interneuron under current clamp produced IPSCs in the postsynaptic granule cell, voltage clamped at -60 mV. All data are mean [plusminus] SEM, with values for FS given first. Statistical significance (p [lt] 0.05) was judged by two-tailed unpaired t-tests.
RESULTS: Interneuron types were distinguished by their responses to current injection (1 sec, + 1 nA). FS neurons (n = 16-20) responded with a continuous spiketrain (72 [plusminus] 5 spikes, 81 [plusminus] 4 Hz mean rate) with modest accommodation. NFS neurons (n = 5-14) accommodated rapidly and completely (14 [plusminus] 3 spikes, 65 [plusminus] 4 Hz mean). FS and NFS neurons had similar resting potentials (FS: 58 [plusminus] 1, NFS: 55 [plusminus] 1 mV), but significantly different input resistances (105 [plusminus] 6 vs 202 [plusminus] 16 MOhm), membrane time constants (33 [plusminus] 3 vs 49 [plusminus] 2 ms), first spike amplitudes (114 [plusminus] 4 vs 125 [plusminus] 2 mV) and spike widths (0.9 [plusminus] 0.08 vs 1.42 [plusminus] 0.18 ms). Both FS and NFS somata were located at the GC layer-hilus border with dendrites in the hilus and molecular layer. All FS cell axons arborized extensively in the granule cell body layer as expected for basket or axo-axonic cells, whereas all NFS axons arborized exclusively in the molecular layer where GC dendrites lie. Measures of presynaptic function revealed that NFS cells had longer synaptic latencies (1.1 [plusminus] 0.1 vs 1.7 [plusminus] 0.1 ms), greater paired pulse depression (14 [plusminus] 2 vs 21 [plusminus] 3 %, 100 ms intervals) and a higher failure rate (48 [plusminus] 6 vs 69 [plusminus] 4 %). However, IPSCs mediated by FS and NFS cells were similar in conductance (2.0 [plusminus] 0.5 vs 0.95 [plusminus] 0.17 nS) and mean decay time constant (23 [plusminus] 0.9 vs 24 [plusminus] 1.3 ms), differing mainly in their rise time constants (0.9 [plusminus] 0.1 ms, 1.8 [plusminus] 0.2), possibly due to dendritic filtering.
CONCLUSIONS: Somatic and dendritic inhibition are mediated by interneurons with distinct electrical and presynaptic properties, whereas individual IPSCs mediated by the two classes are remarkably similar. Thus, differences in the character of somatic versus dendritic inhibition will depend on how these interneurons are driven within the network, rather than on postsynaptic differences at the synapses they form with GCs.
[Supported by: This work was supported by the Epilepsy Foundation (M.V.J.)]