Synaptic Communication among Hippocampal Interneurons: Properties of Spontaneous IPSCs in Morphologically Identified Cells

Abstract

The properties of spontaneous IPSCs (sIPSCs) recorded with whole-cell patch-clamp techniques were investigated in various anatomically identified hippocampal CA1 interneurons and were compared with those recorded in pyramidal cells. Neurons labeled with biocytin or neurobiotin were classified on the basis of their dendritic and axonal arborizations, leading to the identification of previously unknown interneuron types projecting to the dendritic region of pyramidal cells. In most interneurons, the average sIPSCs decayed slower than did those observed in pyramidal cells. The properties of sIPSCs were homogeneous within a given morphologically identified neuron type. Many interneurons had comparable somatic size, location, and dendritic arbor but displayed extremely different axonal projections paralleled by distinct sIPSC properties. Thus, physiological comparisons are only meaningful after the complete morphological identification of the recorded cells. The decay of sIPSCs matched for amplitudes and rise times could vary over 10-fold in a given interneuron, consistent with electrotonic filtering and possibly with different GABA A receptor subunit assemblies present at distinct synapses. Our findings demonstrate an extensive connectivity among hippocampal interneurons through GABA A synapses of various properties that may underlie complex network oscillations at different frequencies.

Roller Coaster Scanning reveals spontaneous triggering of dendritic spikes in CA1 interneurons

“…1 A-C), of which 13 cells were anatomically identified as dendrite-targeting inhibitory cells (25) (SI Materials and Methods). Roller Coaster Scanning provided on average an approximately 27-fold increase in access rate to dendritic segments of this length (Fig.…”

Networks of interneurons with fast and slow γ-aminobutyric acid type A (GABA A ) kinetics provide substrate for mixed gamma-theta rhythm

“…Experimental evidence in support of this connection awaits unambiguous identification of the GABA A,slow population (see below). Circumstantially, fast spontaneous IPSCs are seen in interneurons throughout the hippocampus (26), but only at low rates in SL-M interneurons (27), which may correspond to the GABA A,slow cells. In our model, connections from GABA A,slow to GABA A,fast cells are crucial for supporting either the generation or resynchronization of the theta-gamma rhythm.…”

“…This discrepancy may be caused by the difficulty in distinguishing between fast and slow inputs under current clamp, or by the possibility that the presynaptic cells from the dual-cell recordings may not be the same ones activated by an extracellular stimulus in SL-M. It should also be noted that GABA A,slow spontaneous IPSCs have not been reported in recordings from interneurons (26). Their absence in published data may reflect a rarity of spontaneous activity in GABA A,slow interneurons, as implied by the rarity (but documented presence) of spontaneous GABA A,slow IPSCs in recordings from pyramidal cells (18).…”

“…2), parameters must be tuned to give strong interconnections among cells of the same kinetic class; appropriate levels of drive to each population to give firing rates (under conditions of inhibition) that are compatible with the speed of decay of GABA A,fast or GABA A,slow inhibition, and tuning of the connections from GABA A,slow to GABA A,fast cells to create a pause of the appropriate duration in activity of GABA A,fast cells. In models including connections from GABA A,fast to GABA A,slow cells, as is likely the case in the biological network (21,26), parameters must be tuned even more carefully, with strong connections between cells of a given class, weaker connections between classes, and precise values of drive. Slight mistuning leads to a population rhythm that is dominated by one population or the other (e.g., Fig.…”

Orthogonal arrangement of rhythm-generating microcircuits in the hippocampus

“…The decay time of the I inhibitory postsynaptic potentials (IPSPs) are chosen to be 10 ms (24). The IPSPs originating from the O cells onto pyramidal cells was taken to be 20 ms (25). The decay time of the excitatory postsynaptic potentials onto O and I cells was taken to be 4 ms.…”