α1-Adrenergic Receptors in Neurotransmission, Synaptic Plasticity, and Cognition

Abstract

α₁-adrenergic receptors are G-Protein Coupled Receptors that are involved in neurotransmission and regulate the sympathetic nervous system through binding and activating the neurotransmitter, norepinephrine, and the neurohormone, epinephrine. There are three α₁-adrenergic receptor subtypes (α_1A, α_1B, α_1D) that are known to play various roles in neurotransmission and cognition. They are related to two other adrenergic receptor families that also bind norepinephrine and epinephrine, the β- and α₂-, each with three subtypes (β₁, β₂, β₃, α_2A, α_2B, α_2C). Previous studies assessing the roles of α₁-adrenergic receptors in neurotransmission and cognition have been inconsistent. This was due to the use of poorly-selective ligands and many of these studies were published before the characterization of the cloned receptor subtypes and the subsequent development of animal models. With the availability of more-selective ligands and the development of animal models, a clearer picture of their role in cognition and neurotransmission can be assessed. In this review, we highlight the significant role that the α₁-adrenergic receptor plays in regulating synaptic efficacy, both short and long-term synaptic plasticity, and its regulation of different types of memory. We will also present evidence that the α₁-adrenergic receptors, and particularly the α_1A-adrenergic receptor subtype, are a potentially good target to treat a wide variety of neurological conditions with diminished cognition.

Keywords: G-protein coupled receptor; adrenergic receptor; cognition; neurotransmission; synaptic plasticity.