Why brain plasticity is key to memory and mental health
We recall specific events thanks to networks of neurons encoding information about them and a key process called ‘neuronal plasticity’ shaping what we then remember. But according to Pico Caroni, coordinator of the European Research Council funded MemoryDynamics project, “Many processes happen under the radar, with few distinct measurables for researchers to study with techniques like real-time imaging.” Using mouse models, MemoryDynamics investigated the cellular components involved in the long-term consolidation of memories, and how these change over time. The team found that neural plasticity continued 12 hours after an event, long after initial memory consolidation. This was evidenced in the infralimbic cortex with reversal learning, where responses to an event, such as fear, can be altered when remembering that event. “It is remarkable that brain networks can be recruited or modified during long-term memory consolidation, suggesting that memories consolidated on the day of a learning event can be changed afterwards,” remarks Caroni from project host the Friedrich Miescher Institute for Biomedical Research. Learning was found to be followed by a 5-6 hour period during which subsequent experience can be associated with the initial learning event, effectively combining memories: “Possibly to fit memories into a broader experiential context,” adds Caroni. This was reflected in lab observations where transcription factors known as cFos, which control genes, continued to be expressed in the relevant neuronal networks – a good indicator of ongoing cellular plasticity.
What happens to memories over time?
Physiologically, brain plasticity includes structurally modifying pre-existing synapses to make them stronger or weaker, creating new ones and/or destroying pre-existing ones. Altering how neuronal networks perform means that memory is not just about ‘remembering’ but actively preparing responses to future experiences. “Most of these memory consolidation processes are like cascades lasting for hours, or even days, after the initial learning event,” explains Caroni. Short-term memory plasticity lasts mere seconds or minutes, when signals are processed by synapses and ion channels. Medium-term, over hours, the brain replays the same, but accelerated, patterns of neuronal activity from the original event. Longer-term memory consolidation, 12-15 hours after an event, typically involves a mix of these activities. The cellular processes include the expression of genes within neuronal networks that ensure signalling changes are converted into long-lasting cellular changes, in turn modifying memories. MemoryDynamics used genetic manipulation tools to influence the function of neurons in specific brain areas in mice. The team followed the memory consolidation processes in hippocampal subdivisions; prefrontal cortical areas, including the prelimbic cortex and infralimbic cortex; cortical areas associated with the hippocampus, such as the retrosplenial cortex; and networks important for flexible learning.
Implications for mental health
An unexpected finding concerned changes to gene expression in special neurons called PV+ interneurons. While key to learning, the team discovered that changes in these only manifest hours after learning, suggesting a period where these neurons are especially malleable.
The implication for human health is significant.
There is a brief 10-day window when the functional link in the brain between the ventral hippocampus and prelimbic cortex is critical for prefrontal development. By manipulating the PV+ interneurons in late adolescence to consolidate connections along this brain axis, the team prevented schizophrenia-like symptoms in a genetically predisposed mouse. The technique also showed promise in a mouse model of autism. “We didn’t anticipate that brain mechanisms associated with long-term memory consolidation would have a dramatic impact on the functionality of networks relevant to mental health. This will now be our focus,” concludes Caroni.
Keywords
MemoryDynamics, neuron, brain, plasticity, memory, synapse, mental health, autism, schizophrenia, genetic
