23 research outputs found
A Model of Late Long-Term Potentiation Simulates Aspects of Memory Maintenance
Late long-term potentiation (L-LTP) appears essential for the formation of
long-term memory, with memories at least partly encoded by patterns of
strengthened synapses. How memories are preserved for months or years, despite
molecular turnover, is not well understood. Ongoing recurrent neuronal
activity, during memory recall or during sleep, has been hypothesized to
preferentially potentiate strong synapses, preserving memories. This hypothesis
has not been evaluated in the context of a mathematical model representing
biochemical pathways important for L-LTP. I incorporated ongoing activity into
two such models: a reduced model that represents some of the essential
biochemical processes, and a more detailed published model. The reduced model
represents synaptic tagging and gene induction intuitively, and the detailed
model adds activation of essential kinases by Ca. Ongoing activity was modeled
as continual brief elevations of [Ca]. In each model, two stable states of
synaptic weight resulted. Positive feedback between synaptic weight and the
amplitude of ongoing Ca transients underlies this bistability. A tetanic or
theta-burst stimulus switches a model synapse from a low weight to a high
weight stabilized by ongoing activity. Bistability was robust to parameter
variations. Simulations illustrated that prolonged decreased activity reset
synapses to low weights, suggesting a plausible forgetting mechanism. However,
episodic activity with shorter inactive intervals maintained strong synapses.
Both models support experimental predictions. Tests of these predictions are
expected to further understanding of how neuronal activity is coupled to
maintenance of synaptic strength.Comment: Accepted to PLoS One. 8 figures at en
Adaptations and pathologies linked to dynamic stabilization of neural circuitry
Abstract Brain circuits for infrequently employed memories are reinforced largely during sleep by self-induced, electrical slow-waves, a process referred to as "dynamic stabilization" (DS). The essence of waking brain function in the absence of volitional activity is sensory input processing, an enormous amount of which is visual. These two functions: circuit reinforcement by DS and sensory information processing come into conflict when both occur at a high level, a conflict that may have been the selective pressure for sleep's origin. As brain waves are absent at the low temperatures of deep torpor, essential circuitry of hibernating small mammals would lose its competence if the animals did not warm up periodically to temperatures allowing sleep and circuit reinforcement. Blind, cave-dwelling vertebrates require no sleep because their sensory processing does not interfere with DS. Nor does such interference arise in continuously-swimming fishes, whose need to process visual information is reduced greatly by life in visually relatively featureless, pelagic habitats, and by schooling. Dreams are believed to have their origin in DS of memory circuits. They are thought to have illusory content when the circuits are partially degraded (incompetent), with synaptic efficacies weakened through infrequent use. Partially degraded circuits arise normally in the course of synaptic efficacy decay, or pathologically through abnormal regimens of DS. Organic delirium may result from breakdown of normal regimens of DS of circuitry during sleep, leaving many circuits incompetent. Activation of incompetent circuits during wakefulness apparently produces delirium and hallucinations. Some epileptic seizures may be induced by abnormal regimens of DS of motor circuitry. Regimens of remedial DS during seizures induced by electroconvulsive therapy (ECT) apparently produce temporary remission of delirium by restoring functional or 'dedicated' synaptic efficacies in incompetent circuitry. Sparing of sensory circuitry in fatal familial insomnia seemingly owes to supernormal circuit use in the virtual absence of sleep. ECT shocks and cardioverter defibrillation may have analogous remedial influences.