The logic of inhibitory connectivity in the neocortex

Abstract

Although inhibition plays a major role in the function of the mammalian neocortex, the circuit connectivity of GABAergic interneurons has remained poorly understood. The authors review recent studies of the connections made to and from interneurons, highlighting the overarching principle of a high density of unspecific connections in inhibitory connectivity. Whereas specificity remains in the subcellular targeting of excitatory neurons by interneurons, the general strategy appears to be for interneurons to provide a global "blanket of inhibition" to nearby neurons. In the review, the authors highlight the fact that the function of interneurons, which remains elusive, will be informed by understanding the structure of their connectivity as well as the dynamics of inhibitory synaptic connections. In a last section, the authors describe briefly the link between dense inhibitory networks and different interneuron functions described in the neocortex.

Keywords: GABAergic; connectivity; inhibition; interneurons; networks.

Figure 1

Different pyramidal cell subcompartments targeting GABAergic interneurons. Representation of the different interneuron subtypes based on their pyramidal cell (grey) subcompartment targeting. The parvalbumin-positive basket cells (purple) target the perisomatic region, somatostatin-positive Martinotti cells (green) target the dendrites, and chandelier cells (blue) the axon initial segment. A representative morphological reconstruction of each neuronal subtype from layer 2/3 illustrates their dendritic (black) and axonal (colored) arborizations.

Figure 2

Inhibitory connectivity. (A) Schematic diagram representing the organization of cortical connections between layer 4 and layer 2/3 somatosensory cortex. Excitatory connections define groups of selectively interconnected neurons (red or blue) whereas interneurons (IN) do not respect the fine-scale interconnected cell groups defined by excitatory connections and contact both blue and red pyramidal cell (PC) subpopulations (From Yoshimura and others 2005 with permission). (B) Plots of the connection probability between somatostatin (SOM)-positive interneurons in frontal cortex layer 2/3 and parvalbumin (PV)-positive interneurons in frontal and somatosensory cortex layers 2/3 and 5 and PCs depending on the intersomatic distances. The probability of connectivity from interneurons to PCs is very high when the intersomatic distance between the neurons is low and drops off as the intersomatic distance increases (Adapted from Fino and Yuste 2011 and Packer and Yuste 2011). (C) Schematic representation of a dense connectivity of inhibitory inputs from interneurons to PC (connected interneurons in red and unconnected interneurons in blue). The two PCs illustrate that this applies for connected or unconnected PCs (Adapted from Fino and Yuste 2011). (D) Laminar model of interneuron projections to PCs allowing specific targeting of PC subcompartments: by projecting to layer 1, where only distal dendrites are present, SOM interneurons interneurons avoid contacting somata and proximal dendrites of PCs. PV interneurons, on the other hand, project to layer 2/3 and thus avoid contacting distal dendrites (Adapted from Packer and others, in press).

Figure 3

Short term-dynamics between interneurons and excitatory neurons. (A) Inhibitory postsynaptic potentials (IPSPs) evoked by parvalbumin (PV) cells and somatostatin (SOM) cells onto pyramidal cells (PCs) have distinctive short-term dynamics. Representative IPSPs for each interneuron-PC connections in response to a 40-Hz train (8 spikes) and summary graph of response amplitudes (normalized to the first IPSP) during trains evoked at various frequencies. (B) Excitatory postsynaptic potentials (EPSPs) recorded from PV and SOM interneurons have distinctive short-term dynamics. Representative EPSPs for each interneuron-PC connections in response to a 40-Hz train (8 spikes) and summary graph of response amplitudes (normalized to the first EPSP) during trains evoked at 10 or 40 Hz. For connections in both directions, PV cells display a strong short-term depression whereas SOM interneurons display short-term facilitation (From Beierlein and others 2003 with permission).

Figure 4

Connectivity motifs involving interneurons. Schematic representation of different connectivity configurations allowing various functions described for inhibitory interneurons: feedback, feedforward, or disynaptic inhibition and disinhibition. Pyramidal cells are in grey and interneurons in red.

Figure 5

Dense inhibitory connectivity related to interneuron function. (A) Left: OGB-1–labeled neurons, including four parvalbumin (PV) neurons (red) in layer 2/3. Middle panel: average calcium traces from three PV neurons (red) and two parvalbumin-negative neurons (putative pyramidal cells [PCs], green) during stimulation with episodically presented drifting gratings (eight different drifting grating directions shown at the top). Orientation selectivity index (OSI) for PCs (green) and PV interneurons (red): OSI shows highly selective, sharply tuned PCs, whereas PV cells are broadly tuned and nonselective. This indicates that PV cells are not involved in orientation tuning of PCs in visual cortex (From Hofer and others 2011 with permission). (B) Cell-based visual orientation preference map in the mouse visual cortex from in vivo two-photon calcium imaging. Visually responsive cells are colored according to their estimated preferred orientation (color coding shown at top). Broadly tuned cells are shown in white and correspond to GABAergic interneurons. Right: Schematic representation of diverse input to inhibitory interneurons. Excitatory pyramidal cells (triangles) with different preferred orientations (different colors) provide input to an inhibitory interneuron (white circle) (From Bock and others 2011 with permission).