Interacting brain systems modulate memory consolidation

Abstract

Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders.

Figure 1. Schematic diagram depicting the contribution of the nucleus tractus solitarius (NTS) as both a recipient of peripheral inputs from the vagus nerve and a transmitter of these visceral signals to limbic structures that process memory after emotionally arousing events

Feedback regarding fluctuations in peripheral visceral systems are conveyed to the brain via peripheral vagal fibers. The terminals of the vagus nerve synapse directly within the NTS. After activation by vagal afferents, NTS neurons convey information to structures that process memory such as the amygdala, hippocampus and frontal cortex via a polysynaptic pathway to the locus coeruleus (LC). Norepinephrine (NE) is known as one of the primary transmitters to mediate synaptic communication between these structures.

Figure 2. Schematic diagram depicting a theoretical model of how the basolateral complex of the amygdala (BLA) modulates synaptic plasticity in the hippocampus

Contextual/sensory input initiates transcription of the immediate early gene Arc in pyramidal cells of the CA1 region of the dorsal hippocampus. Arc mRNA is transported to the postsynaptic density of synapses stimulated by the novel context. In position to modify engaged synapses, Arc is either translated to protein, and can thus affect the strength of the synapse, or it is degraded. The coincident and long-lasting amygdala response to stress hormones contributes, directly or indirectly (through entorhinal cortex or septal region), to protein synthesis-dependent changes that underlie long-term plasticity and memory by influencing the translation or degredation of Arc, and possibly other plasticity-related proteins. (Hippocampus illustration, Cajal, 1911).