CaMKII requirement for the persistence of in vivo hippocampal mossy fiber synaptic plasticity and structural reorganization

CaMKII Requirement for in Vivo Insular Cortex LTP Maintenance and CTA Memory Persistence

“…In this regard, it has been observed that synaptic potentiation in hippocampal CA1 region is reverted when ant-CaMKIINtide, a noncompetitive inhibitor of CaMKII, is applied during the maintenance phase of CA1-LTP in vitro (Sanhueza et al, 2007 ). Similar results have been observed by our research group when CaMKIINtide is infused in CA3 region during the maintenance phase of in vivo mossy fiber (MF)-LTP (Juárez-Muñoz et al, 2017 ). In a recent study it has been proved that expression of a transient dominant-negative form of CaMKII erases a previously stablished hippocampal-dependent memory, pointing to a role of this molecule for stable memory storage (Rossetti et al, 2017 ).…”

“…Previous studies have revealed an important potential role for CaMKII in memory maintenance but most have been performed in the hippocampus. In this regard, Sanhueza and colleagues, have reported that application of an inhibitor of CaMKII lead to the decrement of synaptic potentiation during the maintenance phase of in vitro N-methyl-D-aspartate (NMDA) receptors dependent LTP in CA1 region (Sanhueza et al, 2007 , 2011 ), and recently our research group has observed similar results in the hippocampal MF pathway in vivo (Juárez-Muñoz et al, 2017 ).…”

“…Moreover, it is known that structural reorganization as a result of activity is required for maintenance of synaptic strength (Lamprecht and LeDoux, 2004 ; Lynch et al, 2007 ). In this regard, it has been demonstrated that CaMKII inhibition during the maintenance phase of MF-LTP prevents the activity-dependent morphological reorganization in this pathway (Juárez-Muñoz et al, 2017 ). In addition, several studies have demonstrated the interaction of CaMKII with actin polymerization (Fink et al, 2003 ; Kim et al, 2015 ), as well as with enzymes of the Rho/Rac family controlling spine dynamics, turnover and morphology (Murakoshi et al, 2011 ).…”

“…To analyze the effect of CaMKII inhibition on the maintenance of Bla-IC-LTP, animals were divided into the following treatment groups: (1) HFS group ( n = 7), which underwent surgery, had electrodes implanted and received high frequency stimulation (HFS) capable of inducing LTP; (2) HFS+CaMKIINtide group ( n = 7), which in the same conditions of HFS group received intracortical microinfusion of myr-CaMKIINtide (5 μM/μl ACSF/.02 μl/min; Sanhueza et al, 2007 ; Juárez-Muñoz et al, 2017 ) prepared with artificial cerebrospinal fluid (ACSF) as vehicle 2 h after HFS delivery; (3) HFS+ACSF group ( n = 7) which under the same conditions as the HFS+CaMKIINtide group, received intracortical microinfusion of ACSF (1 μl); (4) CaMKIINtide group ( n = 7) which had electrodes implanted and without prior manipulation received intracortical microinfusion of myr-CaMKIINtide (5 μM/μl ACSF/0.02 μl/min). In order to analyze the state of phosphorylation of CaMKII in the presence of myrCaMKIINtide, three additional animals from each of HFS+ACSF and HFS+CaMKIINtide groups were decapitated and tissue was obtained 130 min after HFS application (i.e., 10 min after myr-CaMKIINtide administration) (Figure 1A ).…”

“…To evaluate the effect of CaMKII inhibition on the maintenance of CTA-LTM, animals were divided into the following treatment groups: (1) CTA+STM+CaMKIINtide group ( n = 10), which was trained in CTA and was subjected to a short-term memory aversion test (STM) carried out 4.5 h after the acquisition in order to corroborate the association of saccharin with gastric malaise. One day after acquisition rats received bilateral intracortical microinfusion of myr-CaMKIINtide (5 μM/μl ACSF/0.02 μl/min; Sanhueza et al, 2007 ; Juárez-Muñoz et al, 2017 ) prepared with artificial cerebrospinal fluid (ACSF). LTM was assessed 48 h after infusion; (2) CTA+STM+ACSF ( n = 10), which under the same conditions of CTA+STM+CaMKIINtide group received bilateral intracortical microinfusion of ACSF (1 μl); (3) CTA+CaMKIINtide ( n = 10), which was trained in CTA and received bilateral intracortical microinfusion of myr-CaMKIINtide in absence of STM aversion test in order to prevent the inherent interference to retrieval process (Nader and Einarsson, 2010 ); (4) pCTA+STM+CaMKIINtide ( n = 9), which was pseudotrained in CTA (during the conditioning session PBS was delivered instead of LiCl) and received bilateral intracortical microinfusion of myr-CaMKIINtide (Figure 2A ).…”