View source for Modulation of memory

==Involvement of the Amygdala in Memory Modulation==

Extensive evidence that posttraining electrical stimulation of the amygdala (McGaugh & Gold, 1976) can modulate memory suggested that drug and hormone effects on memory may be mediated by influences involving the amygdala. Considerable evidence supports this implication. Further, such modulation involves noradrenergic activation of the amygdala and efferent projections to other brain regions.

<strong>Noradrenergic Influences in the Basolateral Amygdala:</strong> Memory consolidation is modulated by noradrenergic agonists and antagonists infused into the amygdala posttraining (Ellis & Kesner, 1981; Gallagher, et al., 1981). The basolateral complex of the amygdala (BLA) is the critical region; the adjacent central nucleus does not appear to play a significant role. Epinephrine effects on memory are mediated by noradrenergic activation within the amygdala, as intra-amygdala infusions of the -adrenoceptor antagonist propranolol block epinephrine modulation of memory consolidation (Liang et al., 1986). Noradrenergic activation of the BLA also mediates the modulatory effects of other hormones and neurotransmitters on memory. Intra-BLA infusions of GABAergic receptor antagonists enhance memory consolidation and GABAergic receptor agonists impair memory (Brioni et al., 1989). Similarly, when infused into the amygdala posttraining opioid peptidergic antagonists enhance memory and opioid peptidergic agonists impair memory. Further, <math>\beta</math>-adrenoceptor antagonists infused into the amygdala block these effects. Noradrenergic activity within the BLA is also required for mediating the memory-modulatory effect of several other neurotransmitters, including that of dopamine, corticotropin-releasing factor and the opioid-like orphanin FQ/nociceptin (LaLumiere et al., 2004; Roozendaal et al., 2007)

The extensive evidence that adrenoceptor activation within the amygdala modulates memory consolidation suggests that emotionally arousing learning experiences should induce the release of norepinephrine within the amygdala. Findings of studies using in vivo microdialysis and HPLC to measure norepinephrine levels in the amygdala strongly support this implication. Moreover, drugs and hormones that enhance memory potentiate training-induced increases in amygdala norepinephrine levels and drugs that impair memory consolidation decrease norepinephrine levels. Further, inhibitory avoidance training induces a large and sustained increase in norepinephrine release that correlates highly with 24-hr memory (McIntyre et al., 2002). 

<strong>Glucocorticoid Influences in the Basolateral Amygdala:</strong> Glucocorticoids also modulate memory through influences involving the BLA. Disruption of BLA activity blocks the memory-enhancing effects of posttraining systemic injections of glucocorticoids. Furthermore, systemic or intra-BLA infusions of glucocorticoids enhance memory consolidation and such effects require noradrenergic activation within the amygdala (Quirarte et al., 1997). Activation of glucocorticoid receptors in the BLA appears to modulate memory consolidation by potentiating the norepinephrine-signaling cascade through an interaction with G-protein-mediated effects. As with epinephrine, glucocorticoid effects on memory consolidation also involve activation of noradrenergic cell groups in the brain stem that project to the BLA. Posttraining infusions of a glucocorticoid receptor agonist into the NTS enhance memory and intra-BLA infusions of a <math>\beta</math>-adrenoceptor antagonist block the enhancement (Roozendaal et al., 1999). 

<strong>Cholinergic Influences in the Basolateral Amygdala:</strong> Cholinergic activation within the BLA also modulates memory consolidation. Posttraining intra-amygdala infusions of muscarinic cholinergic receptor agonists and antagonists enhance and impair, respectively, memory for many kinds of training. Additionally, lesions of the nucleus basalis, the major source of cholinergic innervation of the BLA, impair inhibitory avoidance retention and posttraining intra-BLA infusions of either the cholinergic agonist oxotremorine or the acetylcholinesterase inhibitor physostigmine attenuate this memory impairment (Power & McGaugh, 2002). 
[[Image:McGaugh-Scholarpedial_Figure_1_b.png|thumb|500px|right|fig1| summarizes the neuromodulatory interactions within the BLA that are involved in regulating memory consolidation.]]
Cholinergic activation within the BLA is critical for enabling glucocorticoid as well as dopamine enhancement of memory consolidation. As cholinergic modulation of memory consolidation does not require concurrent noradrenergic activation, such activation in the BLA appears to act downstream from adrenergic activation (Dalmaz et al., 1993).