Fifty shades of inhibition

Abstract

Inhibitory circuits are essential for brain function. Our understanding of their synaptic organization has advanced extensively with the identification and classification of an impressive variety of neuron groups, receptor types, and patterns of connectivity. However, the conceptual discussion regarding the role of in neural circuits still revolves around the idea that its primary role is to regulate circuit excitability. Here, I will focus on recent findings from cortical circuits and argue that inhibitory circuits are central to the integration of incoming inputs and can promote sophisticated fine-scale control of local circuits. I propose that inhibitory circuits should not be viewed so much as brakes on principal neurons activity, but as primary contributors to a variety of neural network functions.

Figure 1. Summary of current results regarding thalamocortical projections onto inhibitory neurons in four different cortical regions

primary auditory cortex (A1), primary visual cortex (V1), primary somatosensory cortex (S1) and prefrontal cortex (PFC). The dashed lines indicate connections for which the evidence is controversial at the moment. The thickness of the lines indicates differences in reported synaptic strength. CB/CR⁺: calbindin/calretinin expressing inhibitory neurons; PV⁺: parvalbumin expressing inhibitory neurons; SST⁺: somatostating expressing inhibitory neurons; 5HT3⁺: type 3 serotonin receptor expressing inhibitory neurons. In the PFC panel L4 and L6 are in brackets as in this region these layers are not thought to be clearly identifiable.

Figure 2. Crosstalk of excitatory and inhibitory forms of plasticity

The leftmost diagram shows convergent excitatory and inhibitory inputs from a fast spiking neuron (FS) onto a pyramidal neuron (Pyr). The area in the black square is diagrammed in expanded form to show a summary of recent results regarding the interaction between GABAergic and glutamatergic long term potentiation (LTP) co-induced at converging inputs. The induction of GABAergic LTP prevents glutamatergic LTP and favors long term depression (LTD) by decreasing calcium (Ca²⁺) influx through L-type voltage gated calcium channels (L-type VGCC). GABA_A: ionotropic GABA receptor; GABA_B: metabotropic GABA receptor; Gi: inhibitory G protein; NMDA: NMDA receptor; AMPA: AMPA receptor. The red X indicates decreased Ca²⁺ inflow.