Memory reconsolidation and its maintenance depend on L-voltage-dependent calcium channels and CaMKII functions regulating protein turnover in the hippocampus

Abstract

Immediate postretrieval bilateral blockade of long-acting voltagedependent calcium channels (L-VDCCs), but not of glutamatergic NMDA receptors, in the dorsal CA1 region of the hippocampus hinders retention of long-term spatial memory in the Morris water maze. Immediate postretrieval bilateral inhibition of calcium/calmodulindependent protein kinase (CaMK) II in dorsal CA1 does not affect retention of this task 24 h later but does hinder it 5 d later. These two distinct amnesic effects are abolished if protein degradation by proteasomes is inhibited concomitantly. These results indicate that spatial memory reconsolidation depends on the functionality of L-VDCC in dorsal CA1, that maintenance of subsequent reconsolidated memory trace depends on CaMKII, and these results also suggest that the role played by both L-VDCC and CaMKII is to promote the retrieval-dependent, synaptically localized enhancement of protein synthesis necessary to counteract a retrieval-dependent, synaptic-localized enhancement of protein degradation, which has been described as underlying the characteristic labilization of the memory trace triggered by retrieval. Thus, conceivably, L-VDCC and CaMKII would enhance activity-dependent localized protein renewal, which may account for the improvement of the long-term efficiency of the synapses responsible for the maintenance of reactivated long-term spatial memory.

Hippocampal molecular mechanisms involved in the enhancement of fear extinction caused by exposure to novelty

“…The effects of Nife indicate that the processing of both tasks and the processing of their interaction via behavioral tagging are two more learning variables in which L-VDCCs play a necessary role (18); other such variables are discussed elsewhere (29)(30)(31)(32).…”

“…The lack of influence of βLac on the inhibition of the consolidation of extinction by Rapa suggests that this particular effect does not need ongoing protein turnover to the same extent as the others. Roles for the proteasome-ubiquitin system in consolidation and reconsolidation (18,(23)(24)(25), as well as in LTP (26) and in synaptic tagging (27), have been suggested. Recently, Rapa has been reported to inhibit proteasome activity allosterically (28), but the present findings suggest that this might not be a factor in its Fig.…”

“…Recent findings indicate that several hippocampal processes related to learning and memory, such as the reconsolidation of spatial learning, are highly dependent on NMDA glutamate receptors, calcium/calmodulin protein kinase II (CaMKII), and long-term voltage channel blockers (L-VDCCs), which, in turn, rely on the proteasomal degradation of proteins (18). Here, we study the effects of an NMDA blocker, 2-amino-5-phosphono pentanoic acid (AP5); the L-VDCC blocker nifedipine (Nife); a CaMKII inhibitor, the autocamtide-2-related inhibitory peptide (AIP); and the irreversible proteasome blocker β-lactacystin (12, 13) on the interaction between novelty and extinction (11).…”

Computational Analysis of Cholesterol Binding and Pore-Lining Regions in Alpha-Synuclein: Role in Mitochondrial Function

“…Cholesterol-containing pore-lining regions are known to form Ca 2+ ion channels [18,26] which together with the EF-hand in the C-terminal region of the molecule would regulate Ca 2+ movement across the mitochondrial membrane. It has been proposed that memory reconsolidation and its maintenance depend both on voltage-dependent Ca 2+ channels as well as calcium/calmodulindependent protein kinase in the hippocampus [38]. Ion channel formation in plasma/mitochondrial membranes can be facilitated by exercise and account for the increase in both brain cognition and the beneficial effects of physical activity on selective aspects of brain function (cit.…”

Memória: tipos e mecanismos – achados recentes

“…Um dos muitos mecanismos propostos para a persistência envolve a reiteração cíclica da ativação da enzima cálcio-calmodulina quinase II, e da elevação simultânea dos níveis de cAMP (sigla do inglês: cyclic adenosine monophosphate) no hipocampo, após a consolidação. De fato, a ativação dessa enzima no hipocampo é necessária para a manutenção das memórias (Silva et al, 2013).…”