β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

Abstract

Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express b-adrenergic receptors, which are known to play important roles in gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in the brain. In this review, we highlight the contributions of noradrenergic signaling in general and b-adrenergic receptors in particular, toward modulating hippocampal LTP. We focus on the roles of NE and b-adrenergic receptors in altering the efficacies of specific signaling molecules such as NMDA and AMPA receptors, protein phosphatases, and translation initiation factors. Also, the roles of b-adrenergic receptors in regulating synaptic "tagging" and "capture" of LTP within synaptic networks of the hippocampus are reviewed. Understanding the molecular and cellular bases of noradrenergic signaling will enrich our grasp of how the brain makes new, enduring memories, and may shed light on credible strategies for improving mental health through treatment of specific disorders linked to perturbed memory processing and dysfunctional noradrenergic synaptic transmission.Synaptic plasticity is a fundamental property of nervous system function. A neuron's ability to alter the strength of its synaptic connections is thought to be the foundation for multiple processes, including learning and memory. Synaptic plasticity is not a single, unitary cellular process, but rather an extremely diverse phenomenon that encompasses many forms and functions. Synapses are dynamic by nature, and only through elucidation of the mechanisms that govern their organization and reorganization can we hope to fully understand how the brain processes and stores information.Acting as potent regulatory agents, neuromodulatory transmitters can significantly alter the properties of neurons at cellular and network levels. Specifically, the modulatory role of the noradrenergic system has been extensively characterized, in part because of the system's anatomically ubiquitous connections. Noradrenergic fibers originate mainly in the locus coeruleus (LC) and project widely throughout the forebrain, with dense innervation of the hippocampus, amygdala, and thalamus (Sara 2009). These connections, especially within the hippocampus, strongly modulate synaptic strength and neural network physiology, which lead to significant alterations in learning, memory, attention, and perception. Noradrenergic receptor signal...

Dopamine cross‐reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation

“…Peak dopamine concentration in the synaptic cleft may reach the 10 lM range (Fisher, Morris, Alpert, & Fischman, 1995), suggesting that dopamine could transiently activate b adrenoreceptors in perisynaptic astrocytic domains of dopaminergic synapses. b adrenoreceptors have been implicated in facilitating LTP induction, memory acquisition and retrieval (O'Dell, Connor, Guglietta, & Nguyen, 2015), but their importance is usually discussed in the context of their neuronal function. Astrocytic b adrenoreceptors-despite being highly expressed in these cells (Hertz, Chen, Gibbs, Zang, & Peng, 2004)-have received relatively little attention as players in normal and pathological CNS function.…”

Adrenergic Gate Release for Spike Timing-Dependent Synaptic Potentiation

“…This SAP97-dependent adrenergic modulation integrates the internal state of the brain as a third factor into synaptic plasticity. Since learning is facilitated during attentional and emotional arousal, when noradrenaline is released, synaptic plasticity with all these three factors might better represent behaviorally relevant mechanisms (O’dell et al, 2015; Pawlak et al, 2010; Sara and Bouret, 2012). …”

“…Associative learning is facilitated by aroused attentional or emotional states, involving activation of adrenergic signaling (O’dell et al, 2015). While the expression of STD long-term potentiation (LTP) at excitatory synapses is facilitated by β-adrenergic signaling-mediated priming of synaptic insertion of AMPA-type glutamate receptors (AMPARs; Hu et al, 2007; Makino et al, 2011; Seol et al, 2007), the induction of LTP can also be facilitated by this signaling.…”

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“…17). However, in addition to being expressed in pre-and postsynaptic compartments of neurons, βARs are also found in other cell types, particularly in astrocytes (18)(19)(20)(21).…”