Neocortical interneurons: from diversity, strength

Abstract

Interneurons in the neocortex of the brain are small, locally projecting inhibitory GABAergic cells with a broad array of anatomical and physiological properties. The diversity of interneurons is believed to be crucial for regulating myriad operations in the neocortex. Here, we describe current theories about how interneuron diversity may support distinct neocortical processes that underlie perception.

Figure 1. Interneuron Sensitivity and Sensory Input

(Top) Sensory input to the neocortex, relayed through the thalamus, activates interneurons directly and by relay through adjacent excitatory cells. These interneurons, which produce the inhibitory neurotransmitter GABA, in turn suppress excitatory neurons. (Bottom) Response curves are shown for six hypothetical interneuron types (A1–B3) that require different levels of excitatory input to be activated (that is, to fire an action potential) and that subsequently generate a different amount of inhibition in their excitatory neuron targets. (Middle panels) According to one theory, interneuron diversity keeps excitatory neuron responses constant across a broad range of sensory stimulus conditions. In this example, the six interneuron types provide balancing inhibition to the excitatory cell as excitation increases. The right-hand panel shows that because of the balancing inhibition generated by different interneuron types, there is a constant output from a given excitatory cell, despite a wide range of different inputs. Although the more abstract example of excitatory response amplitude is shown, this kind of balance could maintain constancy in other features. Such features could include keeping the sensitivity of an excitatory neuron to a specific sensory input intact across conditions, for example, when looking at the same face during a real interaction or when viewing it in a photograph. (Bottom panels) In contrast, interneuron diversity in response to sensory excitation may shift the operating mode of the neocortex. In this example, under conditions of lower sensory input, interneurons A1–A3 (green) would be recruited and would place excitatory neurons in a distinct processing mode (mode A). In this example, under conditions of low activation, excitatory neurons show a relatively strong response because the inhibition generated by the interneurons that are recruited is weak. This more permissive environment may enable excitatory neurons to be responsive to a broader range of sensory inputs thus facilitating the detection of stimuli in a perceptual environment. Under conditions of high sensory input, interneurons B1–B3 (blue) would be recruited, and the stronger inhibition they generate would cause excitatory neurons to show a relatively weaker response to input (mode B). The greater suppression generated by B1–B3 interneurons could create greater selectivity for different sensory inputs, facilitating discrimination of these inputs. These two conceptions (middle, bottom) of the role of interneuron diversity in shaping sensory responses are not inherently opposed. Within a class (A or B), interneuron diversity may provide for constancy in excitatory response properties. When a critical level of drive is reached, the neocortex then switches to a different processing mode (from A to B) by recruiting a different class of interneuron.