Neurobiological Principles: Neurotransmitters

To integrate sensory and memory information, to control behavior, and to regulate various metabolic processes in favor of homeostasis, the central nervous system has to perform a huge amount of computations at once. This task is fulfilled by intra- and intercellular signaling cascades driven by a sophisticated network of highly connected neural cells. Most prominently, the release of neurotransmitters into the synaptic cleft is considered to be the key element core of neuronal intercellular communication. This core process of neuronal communication makes the synapse the substantial unit of neurotransmission. Consequently, neurons are thought to establish the foundation of efficient communication within their networks by strengthening and promoting the molecular structures of this functional unit. In the classic view of chemical neurotransmission, the synapse requires (1) the availability for synthesis of the respective neurotransmitter; (2) an activity-responsive, tightly regulated vesicular release machinery on the presynaptic side; (3) postsynaptic receptors, which are selectively activated upon binding by neurotransmitters and subsequently trigger intracellular signaling cascades; and (4) mechanisms to successfully terminate neurotransmission by removal of neurotransmitters from their site of action. With advanced experimental methods and interdisciplinary research approaches, our knowledge on neurotransmission is constantly growing. As a result, the once classical view on neurotransmission is changing in the light of new insights into regulation and organization of synaptic activity. The following sections first give a brief overview on elements determining neurotransmission, the axon initial segment, and presynaptic cytomatrix active zone, before focusing on simultaneous release of two chemically distinct neurotransmitters and neurotransmitter activity beyond synaptic structures (Fig. 1). © Springer Nature Switzerland AG 2022.