Neuroplasticity regulation by noradrenaline in mammalian brain

Abstract

The neuromodulator noradrenaline (NA) is released in almost all brain areas in a highly diffused manner. Its action is slow, as it acts through G protein-coupled receptors, but its wide release in the brain makes NA a crucial regulator for various fundamental brain functions such as arousal, attention and memory processes [102]. To understand how NA acts in the brain to promote such diverse actions, it is necessary to dissect the cellular actions of NA at the level of single neurons as well as at the level of neuronal networks. In the present article, we will provide a compact review of the main literatures concerning the NA actions on neuroplasticity processes. Depending on which subtype of adrenoceptor is activated, NA differently affects intrinsic membrane properties of postsynaptic neurons and synaptic plasticity. For example, beta-adrenoceptor activation is mainly related to the potentiation of synaptic responses and learning and memory processes. alpha2-adrenoceptor activation may contribute to a high-order information processing such as executive function, but currently the direction of synaptic plasticity modification by alpha2-adrenoceptors has not been clearly determined. The activation of alpha1-adrenoceptors appears to mainly induce synaptic depression in the brain. But its physiological roles are still unclear: while its activation has been described as beneficial for cognitive functions, it may also exert detrimental effects in some brain structures such as the prefrontal cortex.

Keywords: LTD; LTP; Noradrenaline; neuromodulation; synaptic plasticity..

Fig. (1). Schematic representations of the action of adrenoceptors that induce intrinsic plasticity.

a. β-adrenoceptor activation generally induces depolarization of postsynaptic neurons with an increase of input resistance. It reduces K⁺ currents (1) and facilitates Ih current via cAMP pathway (2) and the entry of Ca²⁺ (3). b. α₁-adrenoceptors can also induce depolarization of neurons with an increase of input resistance. They reduce K⁺ currents (1) and act on Ca²⁺ entry via the activation of phosphoinositide turnover (2). c. α₂-adrenoceptors generally induce hyperpolarization coupled to an increase or decrease of input resistance via blockade of Ih current (2) or opening of K⁺ channels (1) respectively. They also inhibit Ca²⁺ channels (3). AC, adenylate cyclase; ATP, adenosine triphosphate; Ca²⁺, calcium; cAMP, cyclic adenosine monophosphate; DAG, diacylglyrerol; Ih, hyperpolarization-activated currents; IP3, inositol (1,4,5)-trisphosphate; K⁺, potassium; PIP2, phosphatidylinositol biphosphate; PLCβ, phospholipase Cβ.