Biology subjects

Alberini, C.

Publications and source records attributed to Alberini, C..

3 recordsLinked to original sources

bioRxiv2022

Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: critical roles of CaMKIIα and MeCP2

Key features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) dependent feedback loops. We investigated the ways in which these pathways may contribute to developmental and dynamical features of consolidation. A computational model of molecular processes underlying consolidation following inhibitory avoidance (IA) training in rats was developed. Differential equations described the actions of CaMKII, multiple feedback loops regulating BDNF expression, and several transcription factors including methyl-CpG binding protein 2 (MeCP2), histone deacetylase 2 (HDAC2), and SIN3 transcription regulator family member A (Sin3a). This model provides novel explanations for the (apparent) rapid forgetting of infantile memory and the temporal progression of memory consolidation in adults. Simulations predict that dual effects of MeCP2 on the expression of bdnf, and interaction between MeCP2 and CaMKII, play critical roles in the rapid forgetting of infantile memory and the progress of memory resistance to disruptions. These insights suggest new potential targets of therapy for memory impairment. Author SummaryLong-term memories (LTMs) are enduring and resistant to disruption These features are acquired via processes collectively referred to as consolidation. In adults, the initial stages of consolidation follow complex dynamics that are believed to emerge from interacting biochemical signaling pathways [1], including BDNF and CaMKII dependent feedback loops. Similarly, the acquisition of ability to consolidate memory in infantile animals is believed to emerge from the functional maturation of these molecular pathways [2]. Here, the ways in which these pathways contribute to consolidation were investigated using a computational model. This model provides novel explanations for the apparent rapid forgetting of infantile memory and for development of resistance to disruption during memory consolidation.

neuroscience↗

bioRxiv2021

Neuronal activity-driven oligodendrogenesis in selected brain regions is required for episodic memories

The formation of long-term episodic memories requires the activation of molecular mechanisms in several regions of the medial temporal lobe, including the hippocampus and anterior cingulate cortex (ACC). The extent to which these regions engage distinct mechanisms and cell types to support memory formation is not well understood. Recent studies reported that oligodendrogenesis is essential for learning and long-term memory; however, whether oligodendrocyte lineage cells are required only in selected brain regions is still unclear. Also still unknown are the temporal kinetics of oligodendrocyte lineage cells involvement in memory processes and whether these cells are engaged in response to neuronal activity. Here we show that in rats and mice, episodic learning rapidly increases the oligodendrogenesis and myelin biogenesis transcripts Olig2, Myrf, Mbp, and Plp1 as well as oligodendrocyte precursor cells (OPC) proliferation and differentiation in the ACC, but not in the dorsal hippocampus (dHC). Region-specific knockdown or knockout of Myrf, a regulator of oligodendrocyte differentiation, revealed that cells of the oligodendrocyte lineage are required for memory formation in the ACC but not the dHC. Chemogenetic neuronal silencing in the ACC showed that neuronal activity is critical for learning-induced OPC proliferation. Hence, activity-driven oligodendrocyte lineage cells in the ACC, but not dHC, are critical for the formation of episodic memories. Impact statementOligodendrocyte lineage cells are required in the anterior cingulate cortex but not in the hippocampus for long-term memory formation.

neuroscience↗

bioRxiv2017

Experience-induced forgetting by WT1 enables learning of sequential tasks.

Under physiological conditions, strength and persistence of memory must be regulated in order to produce behavioral flexibility. In fact, impairments in memory flexibility are associated with pathologies such as post-traumatic stress disorder or autism; however the underlying mechanisms that enable memory flexibility are still poorly understood. Here we identified the transcriptional repressor Wilms Tumor 1 (WT1) as a critical synaptic plasticity regulator that decreases memory strength, promoting memory flexibility. WT1 was activated in the hippocampus following induction of long-term potentiation (LTP) or learning. WT1 knockdown enhanced CA1 neuronal excitability, LTP and long-term memory whereas its over-expression weakened memory retention. Moreover, forebrain WT1-deficient mice showed deficits in both reversal, sequential learning tasks and contextual fear extinction, exhibiting impaired memory flexibility. We conclude that WT1 limits memory strength or promotes memory weakening, thus enabling memory flexibility, a process that is critical for learning from new experience.

neuroscience↗