Long‐term potentiation and the mechanisms of memory

Abstract

Long-term potentiation (LIP) is a cellular model of the memory processes that occurs in many nerve cells, usually at glutamatergic synapses. For this reason, glutamatergic synapses being the most abundant in the brain, LTP has been widely proposed as a mechanism of memory. Recent findings support this proposal and indicate that, indeed, LTP and memory processes share many properties. The initial steps of LTP and of memory involve the activation of glutamatergic NMDA (N-methyl-D-asprtate) receptors, sensitive to AP5 (amino phosphono valerate), and are very sensitive to inhibition by GABA, (gamma amino butyric acid type A) receptor agonists. The phase that follows in the next 2 or 3 h depends on activation of protein kinase C (PKC) and is sensitive to inhibitors of this enzyme family. Like LTP, the underlying mechanism of memories persists for very long periods without the need of expression; and, like LTP, memories are readily expressed upon a reinstatement of the stimuli used in their induction, as i s the case in test sessions. The expression of LTP and the expression of memory rely on AMPA (D,L-alpha-amino hydroxy methyl isoxazolone propionate) receptors sensitive to CNQX (cyano nitro quinoxaline dione). LTP occurs in many places within the brain, including the hippocampus, amygala, medial septum, and entorhinal cortex. The drug effects on memory mentioned above are seen when the drugs are infused into these brain regions. The region(s) involved depend on the type of memory being processed. These findings support the idea that LTP underlies memory acquisition, retention, and retrieval (the latter, at least for many days after acquisition) and may provide some clues for the development of drugs to alleviate memory disorders. o 1993 Wiley-Liss, Inc.

Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat

“…When dosed only prior to the acquisition trial (T1) or the retention trial (T2), CX691 significantly attenuated the temporal deficit, suggesting that it is exerting its pro-cognitive effects by enhancing both acquisition and retention/retrieval of the information. This is consistent with literature suggesting that AMPA receptors might be involved in both acquisition and retrieval processes (Izquierdo 1993;Danysz et al 1995). By contrast, a previous study suggested that an alternative AMPA receptor positive modulator, S-18986, affected only retrieval processes when tested in this task (Lebrun et al 2000).…”

Scopolamine model of dementia: electroencephalogram findings and cognitive performance

“…Dunnett & Robbins [ 31] suggested that the dopaminergic system is related to visual processing and attention. Excitatory amino acid receptor agonists such as glutamate showed adverse effects: long‐term potentiation has been suggested to be the physiological correlate of memory formation [ 32]. On the other hand, high levels of glutamate are neurotoxic [ 33].…”

Effect of repeated restraint stress on memory in different tasks

“…The hippocampus plays important roles in cognition and neuroendocrine function (13,19), and is known to be important for the consolidation of memories in different tasks, including the tasks studied in this report (27). It should be noted that while deleterious effects of excess glucocorticoid on the brain have been shown, there is little evidence indicating whether brain function itself is compromised in a situation of repeated stress.…”

“…Moreover, many studies have provided evidence that glucocorticoids regulate learning and memory (5,(7)(8)(9)(10). It has also been shown that stress impairs hippocampal long-term potentiation (LTP) (11,12), a long-lasting increase in synaptic excitability that might be involved in the mechanism of memory storage (13)(14)(15).…”

“…The hippocampus is a critical site for memory (11,13,19), and the loss of hippocampal neurons appears to be associated with the emergence of cognitive deficits in aged rats (16). On the other hand, chronically stressed animals do not experience all the hormonal consequences that animals exposed to a single stress episode do (20,21), and it was suggested that previous exposure to chronic stress modified behavior in a novel stress situation (22,23).…”