Figure 4.

Mechanisms of norepinephrine-mediated lateral inhibition within the Glutamate Amplifies Noradrenergic Effects Framework. While neuronal ensembles transmitting prioritized information are expedited at noradrenergic hot spots (purple), regions containing low levels of norepinephrine and with low or absent glutamatergic input are suppressed. There are two mechanisms by which the noradrenergic system can accomplish this, both involve modulation of GABA-ergic interneurons (red). Depending on the adrenergic receptors expressed, and the concentration of norepinephrine at the synapse, various cellular responses may occur. Two examples are illustrated. The bottom neuronal path shows a cortical interneuron that expresses the α-1-adrenergic receptor (α1-AR) and is activated by moderate levels of norepinephrine. This results in the activation of the Gα_q in the post-synaptic cell, resulting in the depolarization of the GABAergic interneuron and inhibition of the neuronal path. The top neuronal path shows two GABA-ergic interneurons with feed-forward connections that are suppressed when pre-synaptic α2-adrenergic receptors are activated by low levels of norepinephrine, resulting in hyperpolarization and inhibition of neuronal firing. Thus, the varied affinity of the adrenergic receptors for norepinephrine, combined with the presence or absence of glutamate, is the cellular basis for this lateral-inhibition response, and ultimately serves to heighten the response of other neurons to salient information.