Phases Of Memory Processing Research Articles

Locus coeruleus in memory formation and Alzheimer's disease.

Catecholamine neurons of the locus coeruleus (LC) in the dorsal pontine tegmentum innervate the entire neuroaxis, with signaling actions implicated in the regulation of attention, arousal, sleep–wake cycle, learning, memory, anxiety, pain, mood, and brain metabolism. The co‐release of norepinephrine (NE) and dopamine (DA) from LC terminals in the hippocampus plays a role in all stages of hippocampal‐memory processing. This catecholaminergic regulation modulates the encoding, consolidation, retrieval, and reversal of hippocampus‐based memory. LC neurons in awake animals have two distinct firing modes: tonic firing (explorative) and phasic firing (exploitative). These two firing modes exert different modulatory effects on post‐synaptic dendritic spines. In the hippocampus, the firing modes regulate long‐term potentiation (LTP) and long‐term depression, which differentially regulate the mRNA expression and transcription of plasticity‐related proteins (PRPs). These proteins aid in structural alterations of dendritic spines, that is, structural long‐term potentiation (sLTP), via expansion and structural long‐term depression (sLTD) via contraction of post‐synaptic dendritic spines. Given the LC's role in all phases of memory processing, the degeneration of 50% of the LC neuron population occurring in Alzheimer's disease (AD) is a clinically relevant aspect of disease pathology. The loss of catecholaminergic regulation contributes to dysfunction in memory processes along with impaired functions associated with attention and task completion. The multifaceted role of the LC in memory and general task performance and the close correlation of LC degeneration with neurodegenerative disease progression together implicate it as a target for new clinical assessment tools.

Endocannabinoids in nervous system health and disease: the big picture in a nutshell

The psychoactive component of the cannabis resin and flowers, delta9-tetrahydrocannabinol (THC), was first isolated in 1964, and at least 70 other structurally related 'phytocannabinoid' compounds have since been identified. The serendipitous identification of a G-protein-coupled cannabinoid receptor at which THC is active in the brain heralded an explosion in cannabinoid research. Elements of the endocannabinoid system (ECS) comprise the cannabinoid receptors, a family of nascent lipid ligands, the 'endocannabinoids' and the machinery for their biosynthesis and metabolism. The function of the ECS is thus defined by modulation of these receptors, in particular, by two of the best-described ligands, 2-arachidonoyl glycerol and anandamide (arachidonylethanolamide). Research on the ECS has recently aroused enormous interest not only for the physiological functions, but also for the promising therapeutic potentials of drugs interfering with the activity of cannabinoid receptors. Many of the former relate to stress-recovery systems and to the maintenance of homeostatic balance. Among other functions, the ECS is involved in neuroprotection, modulation of nociception, regulation of motor activity, neurogenesis, synaptic plasticity and the control of certain phases of memory processing. In addition, the ECS acts to modulate the immune and inflammatory responses and to maintain a positive energy balance. This theme issue aims to provide the reader with an overview of ECS pharmacology, followed by discussions on the pivotal role of this system in the modulation of neurogenesis in the developing and adult organism, memory processes and synaptic plasticity, as well as in pathological pain and brain ageing. The volume will conclude with discussions that address the proposed therapeutic applications of targeting the ECS for the treatment of neurodegeneration, pain and mental illness.

Molecular motor KIF17 is fundamental for memory and learning via differential support of synaptic NR2A/2B levels

Summary Kinesin superfamily motor protein 17 (KIF17) is a candidate transporter of N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). Disruption of the murine kif17 gene inhibits NR2B transport, accompanied by decreased transcription of nr2b , resulting in a loss of synaptic NR2B. In kif17 −/− hippocampal neurons, the NR2A level is also decreased because of accelerated ubiquitin-proteasome system-dependent degradation. Accordingly, NMDA receptor-mediated synaptic currents, early and late long-term potentiation, long-term depression, and CREB responses are attenuated in kif17 −/− neurons, concomitant with a hippocampus-dependent memory impairment in knockout mice. In wild-type neurons, CREB is activated by synaptic inputs, which increase the levels of KIF17 and NR2B. Thus, KIF17 differentially maintains the levels of NR2A and NR2B, and, when synapses are stimulated, the NR2B/KIF17 complex is upregulated on demand through CREB activity. These KIF17-based mechanisms for maintaining NR2A/2B levels could underlie multiple phases of memory processes in vivo.

The locus coeruleus involves in consolidation and memory retrieval, but not in acquisition of inhibitory avoidance learning task

The locus coeruleus (LC) located at the level of the pons, is involved in cognitive functions such as learning and memory. The bilateral lidocaine-induced reversible inactivation of this nucleus has been considered in order to study its role in the phases of memory processing (acquisition, consolidation and retention) without any interference with the function of the same structure either during earlier and/or later phases of the same process. In this study, inhibitory avoidance (IA) learning task used to find the LC function in acquisition, consolidation and retrieval. Saline or lidocaine 4% (0.5μl/side) microinjected into the LC, for assessing the acquisition (5min before training), consolidation (5, 90 and 360min after training) and memory retrieval, 5min before testing. The retention test was done 24h after learning. Our results indicated that: (1) The bilateral functional inactivation of LC before training did not affect acquisition, but affected subsequent memory retention 24h later in IA task. (2) The lidocaine-induced inactivation of LC only 5min after training impaired consolidation but did not affect it after 90 or 360min. (3) Inactivation of the LC, 5min before pre-retrieval test, impaired memory retrieval in IA task. In conclusion, it seems that the nucleus locus coeruleus does not affect acquisition while it involves in the memory consolidation and retrieval of inhibitory avoidance learning task.