Co-allocation to overlapping dendritic branches in the retrosplenial cortex integrates contextual memories across time

Events occurring close in time are often linked in memory, providing an episodic timeline and a framework for those memories. Recent studies suggest that memories acquired close in time are encoded by overlapping neuronal ensembles, and that this overlap is necessary for memory linking. Transient increases in neuronal excitability drive this ensemble overlap, but whether dendritic plasticity plays a role in linking memories is unknown. Here, we show that contextual memory linking is not only dependent on ensemble overlap in the retrosplenial cortex (RSC), but also on RSC branch-specific dendritic allocation mechanisms. Using longitudinal two-photon calcium imaging of RSC dendrites, we show that the same dendritic segments are preferentially activated by two linked (but not independent) contextual memories, and that spine clusters added after each of two linked (but not independent) contextual memories are allocated to the same dendritic segments. Importantly, with a novel optogenetic tool, selectively targeted to activated dendritic segments following learning, we show that reactivation of dendrites tagged during the first context exploration is sufficient to link two contextual memories. These results demonstrate a causal role for dendritic mechanisms in memory linking and reveal a novel set of rules that govern how linked, and independent memories are allocated to dendritic compartments.

Carthamin yellow protected rats from cerebral ischemia–reperfusion injury by improving neuronal dendritic plasticity via antiferroptosis mediated NF-κB/NLRP3 inflammasome pathway deactivation

Background: Carthamin yellow (CY), a flavonoid compound extracted from safflower, has been reported to attenuate cardiac ischemia and reperfusion injury. It is unclear whether CY could ameliorate ischemic stroke. Methods: We examined the preventive effects of CY in experimental ischemic stroke using middle cerebral artery occlusion (MCAO) rats model. Neurological function, brain edema and infarct area were assessed to elucidate the effects of CY on neurological function and ischemic brain injury. MAP-2 Immunofluorescence activity, expressions in NF-κB/NLRP3 inflammasome pathway and ferroptosis were determined to reveal its underlying mechanism. Results: A 2-week CY treatment attenuated the neurological deficit score, brain water content and infarct area in MCAO rats. Meanwhile, CY intervention increased the MAP-2 Immunofluorescence activity and deactivated NF-κB/NLRP3 inflammasome pathway in the cortex. Declined serum TNF-α, IL-1β and IL-6 concentrations were detected following CY administration. Furthermore, CY treatment inhibited Fe2+ and ROS accumulation, and restored the protein expressions of ACSL4, TFR1, GPX4 and FTH1 in the brain. The levels of GSH, SOD and MDA in the serum were reversed by CY intervention. Conclusion: CY protected rats from ischemic stroke, which was associated with the improvement of neuronal dendritic plasticity through antiferroptosis mediated NF-κB/NLRP3 inflammasome pathway deactivation.

Electroacupuncture Regulates Hippocampal Synaptic Plasticity via miR-134-Mediated LIMK1 Function in Rats with Ischemic Stroke

MircoRNAs (miRs) have been implicated in learning and memory, by regulating LIM domain kinase (LIMK1) to induce synaptic-dendritic plasticity. The study aimed to investigate whether miRNAs/LIMK1 signaling was involved in electroacupuncture- (EA-) mediated synaptic-dendritic plasticity in a rat model of middle cerebral artery occlusion induced cognitive deficit (MICD). Compared to untreatment or non-acupoint-EA treatment, EA at DU20 and DU24 acupoints could shorten escape latency and increase the frequency of crossing platform in Morris water maze test. T2-weighted imaging showed that the MICD rat brain lesions were located in cortex, hippocampus, corpus striatum, and thalamus regions and injured volumes were reduced after EA. Furthermore, we found that the density of dendritic spine and the number of synapses in the hippocampal CA1 pyramidal cells were obviously reduced at Day 14 after MICD. However, synaptic-dendritic loss could be rescued after EA. Moreover, the synaptic-dendritic plasticity was associated with increases of the total LIMK1 and phospho-LIMK1 levels in hippocampal CA1 region, wherein EA decreased the expression of miR-134, negatively regulating LIMK1 to enhance synaptic-dendritic plasticity. Therefore, miR-134-mediated LIMK1 was involved in EA-induced hippocampal synaptic plasticity, which served as a contributor to improving learning and memory during the recovery stage of ischemic stroke.