Biology subjects

Silva, N. T.

Publications and source records attributed to Silva, N. T..

4 recordsLinked to original sources

bioRxiv2024

Behavioral state regulates the dynamics of memory consolidation

Long-term memories are consolidated over time, progressively becoming more stable and resistant to interference. Memory consolidation occurs offline and often involves transfer of memories from one brain site to another. For many motor memories, consolidation is thought to involve early learning in cerebellar cortex that is subsequently transferred to the cerebellar nuclei. Here we report that in mice, engaging in locomotor activity during training in a classical conditioning task shifts the critical time window for memory consolidation, from just after training sessions, to between trials, within sessions. This temporal shift requires natural patterns of cerebellar granule cell activity during intertrial intervals and is accompanied by earlier involvement of the downstream cerebellar nucleus. These results reveal that the critical time window for cerebellar memory consolidation can be surprisingly brief, on a timescale from seconds to minutes, and that it is dynamically regulated by behavioral state.

neuroscience↗

bioRxiv2022

Neural instructive signals for associative cerebellar learning

Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning, and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. Here we used cell-type specific perturbations of climbing fibers, Purkinje cells, and other cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning. Our findings reveal that while optogenetic stimulation of either climbing fibers or Purkinje cells are capable of driving learning under some conditions, even subtle reductions in climbing fiber signaling completely block learning to natural conditioning stimuli. We conclude that climbing fibers and corresponding Purkinje cell complex-spike events provide essential instructive signals for associative cerebellar learning.

neuroscience↗

bioRxiv2019

Changes in behavioral state account for the modulation of cerebellar learning by cannabinoid receptors

Cannabinoids are notorious and profound modulators of behavioral state. In the brain, endocannabinoids act via Type 1-cannabinoid receptors (CB1) to modulate synaptic transmission and mediate multiple forms of synaptic plasticity. CB1 knockout (CB1KO) mice display a range of behavioral phenotypes, in particular hypoactivity and various deficits in learning and memory, including cerebellumdependent delay eyeblink conditioning. Here we find that the apparent effects of CB1 deletion on cerebellar learning are not due to direct effects on CB1-dependent plasticity, but rather, arise as a secondary consequence of altered behavioral state. Hypoactivity of CB1KO mice accounts for their impaired eyeblink conditioning across both animals and trials. Moreover, learning in these mutants is rescued by walking on a motorized treadmill during training. Finally, cerebellar granule cell-specific CB1KOs exhibit normal eyeblink conditioning, and both global and granule cell-specific CB1KOs display normal cerebellum-dependent locomotor coordination and learning. These findings highlight the modulation of behavioral state as a powerful independent means through which individual genes contribute to complex behaviors.

neuroscience↗

bioRxiv2017

Locomotor activity modulates associative learning in mouse cerebellum

Changes in behavioral state are associated with modulation of sensory responses across visual, auditory and somatosensory cortices. Here we show that locomotor activity independently modulates performance in delay eyeblink conditioning, a cerebellum-dependent form of associative learning. Increased locomotor speed in head-fixed mice was associated with earlier onset of learning and trial-by-trial enhancement of learned responses. The influence of locomotion on conditioned responses was dissociable from changes in arousal and was independent of the sensory modality of the conditioned stimulus. Eyelid responses evoked by optogenetic stimulation of mossy fiber terminals within the cerebellar cortex, but not at sites downstream, were also positively modulated by ongoing locomotion. We conclude that locomotor activity modulates delay eyeblink conditioning through mechanisms acting on the mossy fiber pathway within the cerebellar cortex. Taken together, these results suggest a novel role for behavioral state modulation in associative learning and provide a potential mechanism through which engaging in movement can improve an individuals ability to learn.

neuroscience↗