Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations

Abstract

In the cerebral cortex, diverse types of neurons form intricate circuits and cooperate in time for the processing and storage of information. Recent advances reveal a spatiotemporal division of labor in cortical circuits, as exemplified in the CA1 hippocampal area. In particular, distinct GABAergic (gamma-aminobutyric acid-releasing) cell types subdivide the surface of pyramidal cells and act in discrete time windows, either on the same or on different subcellular compartments. They also interact with glutamatergic pyramidal cell inputs in a domain-specific manner and support synaptic temporal dynamics, network oscillations, selection of cell assemblies, and the implementation of brain states. The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior.

Fig. 1

Three types of pyramidal cell are accompanied by at least 21 classes of interneuron in the hippocampal CA1 area. The main termination of five glutamatergic inputs are indicated on the left. The somata and dendrites of interneurons innervating pyramidal cells (blue) are orange, and those innervating mainly other interneurons are pink. Axons are purple; the main synaptic terminations are yellow. Note the association of the output synapses of different interneuron types with the perisomatic region (left) and either the Schaffer collateral/commissural or the entorhinal pathway termination zones (right), respectively. VIP, vasoactive intestinal polypeptide; VGLUT, vesicular glutamate transporter; O-LM, oriens lacunosum moleculare.

Fig. 2

Spatiotemporal interaction between pyramidal cells and several classes of interneuron during network oscillations, shown as a schematic summary of the main synaptic connections of pyramidal cells (P), PV-expressing basket, axo-axonic, bistratified, O-LM, and three classes of CCK-expressing interneurons. The firing probability histograms show that interneurons innervating different domains of pyramidal cells fire with distinct temporal patterns during theta and ripple oscillations, and their spike timing is coupled to field gamma oscillations to differing degrees. The same somatic and dendritic domains receive differentially timed input from several types of GABAergic interneuron (18, 19, 23, 30). ACh, acetylcholine.

Fig. 3

In vivo spike timing of a GABAergic CA1 neuron projecting to the subiculum (Sub), presubiculum (PrS), retrosplenial cortex (RSG), and indusium griseum (IG). (A) The soma, dendrites (red), and axons (yellow) in coronal plains as indicated in (B). CC, corpus callosum. (B) Representation in the sagittal plane, showing the rostrocaudal extent of the cell. The soma is located at the border of the stratum radiatum and lacunosum moleculare. The axon, traced over 5 mm, runs toward caudal regions through the subiculum and presubiculum, then bifurcates into further caudal and rostral branches. Shaded areas represent boutons in the reconstructed sections. (C to G) Soma and dendrites are complete; the axon is shown from selected sections [blocks in (B)]; note few local collaterals within the hippocampus. The axon innervates the molecular layer in the subiculum and the retrosplenial granular cortex. (H) Electron micrograph of a neurobiotin-filled bouton making a type II synapse (arrow) with a dendritic shaft in the subiculum. (I) In vivo firing patterns show that the cell fires at the descending phase of extracellular theta oscillations (filter, direct current to 220 Hz) recorded from a second electrode in the pyramidal layer. During ripple episodes (right upper, 90 to 140 Hz band pass), there is no increase in firing. Scale bars, 100 μm [(C) to (G)], 0.2 μm (H). Calibrations in (I): theta, 0.2 mV; ripples, 0.05 mV, 0.1 s; spikes, 0.5 mV.