Total Number and Ratio of Excitatory and Inhibitory Synapses Converging onto Single Interneurons of Different Types in the CA1 Area of the Rat Hippocampus

Abstract

The least known aspect of the functional architecture of hippocampal microcircuits is the quantitative distribution of synaptic inputs of identified cell classes. The complete dendritic trees of functionally distinct interneuron types containing parvalbumin (PV), calbindin D(28k) (CB), or calretinin (CR) were reconstructed at the light microscopic level to describe their geometry, total length, and laminar distribution. Serial electron microscopic reconstruction and postembedding GABA immunostaining was then used to determine the density of GABA-negative asymmetrical (excitatory) and GABA-positive symmetrical (inhibitory) synaptic inputs on their dendrites, somata, and axon initial segments. The total convergence and the distribution of excitatory and inhibitory inputs were then calculated using the light and electron microscopic data sets. The three populations showed characteristic differences in dendritic morphology and in the density and distribution of afferent synapses. PV cells possessed the most extensive dendritic tree (4300 microm) and the thickest dendrites. CR cells had the smallest dendritic tree (2500 microm) and the thinnest shafts. The density of inputs as well as the total number of excitatory plus inhibitory synapses was several times higher on PV cells (on average, 16,294) than on CB (3839) or CR (2186) cells. The ratio of GABAergic inputs was significantly higher on CB (29.4%) and CR (20.71%) cells than on PV cells (6.4%). The density of inhibitory terminals was higher in the perisomatic region than on the distal dendrites. These anatomical data are essential to understand the distinct behavior and role of these interneuron types during hippocampal activity patterns and represent fundamental information for modeling studies.

Dysfunction of hippocampal interneurons in epilepsy

“…In the dentate hilus of epileptic patients with hippocampal sclerosis, most of the few surviving hilar neurons are CB-IR [39] . Studies have indicated that the density of inputs and the total number of afferent synapses are several times higher on PV cells than on CB or CR cells, whereas the ratio of inhibitory inputs is significantly higher on CB and CR cells [40] , suggesting that PV-positive neurons receive more excitatory inputs than CB-and CR-positive neurons and thus are more vulnerable to excitotoxic damage. The AMPA receptor subunit GluR3 in PV-containing interneurons is highly expressed in the hippocampus and neocortex, whereas GluR2 is not observed, indicating that this is likely to contribute to the selective vulnerability of these interneurons to excitotoxicity [41] .…”

AMPA Receptors and Kainate Receptors Encode Different Features of Afferent Activity

“…Although individual afferent fibers had little effect on membrane potential for either AMPARs or KARs in our model, interneurons receive input from 1000 to 10,000 afferent fibers (Gulyas et al, 1999). To examine the effects of synaptically driven AMPARs and KARs when multiple fibers are active, we considered a model in which a small population of 50 fibers was activated.…”

TrkB signaling in parvalbumin-positive interneurons is critical for gamma-band network synchronization in hippocampus

“…Gamma oscillations are exquisitely susceptible to modulation of the cellular and synaptic mechanisms underlying the rhythmic activity. Fast-spiking PV+ interneurons are the main recipient of recurrent glutamatergic innervations in the hippocampal circuitry, and their role in gamma-frequency synchronization in cortical and hippocampal networks is well-established (34,35). Despite extensive knowledge of the role of BDNF-TrkB signaling in neuronal development and synaptic function, the question of how BDNF might modulate and control rhythmic activity has so far not been answered.…”