Biology subjects

Jayabal, S.

Publications and source records attributed to Jayabal, S..

3 recordsLinked to original sources

bioRxiv2026

α-synuclein pathology drives multi-scale reorganization of fronto-limbic networks and cognitive flexibility in the common marmoset

Understanding how -synuclein misfolding and spreading affect brain systems is central to synucleinopathy research, yet evidence from primate models remains limited. Here, we combined histology, awake structural MRI, awake resting-state fMRI, regional homogeneity, actimetry and touchscreen behavioral testing to longitudinally track the consequences of striatal -synuclein seeding in the common marmoset. Phosphorylated -synuclein inclusions were detected from 2 months post-injection and spread progressively to distributed cortical and subcortical regions bilaterally, accompanied by regionally specific structural atrophy. Functional imaging revealed widespread disruption of large-scale networks, particularly within fronto-limbic circuits, alongside reductions in local functional coherence. Despite the absence of overt motor or sleep deficits, animals exhibited a selective impairment in cognitive flexibility, with preserved learning and task engagement. These findings indicate that striatal -synuclein seeding induces a multi-scale reorganization of brain networks preferentially affecting circuits supporting cognitive flexibility and limbic processing, establishing a primate platform for studying early stages of synucleinopathy.

animal behavior and cognition↗

bioRxiv2022

Experience Adaptively Tunes the Timing Rules for Associative Plasticity

The brain learns about the statistical relationships between events in the world through associative synaptic plasticity, controlled by the timing between neural events. Here, we show that experience can dramatically alter the timing rules governing associative plasticity and learning. In normally reared mice, the timing requirements for short- and long-term associative plasticity at synapses in the oculomotor cerebellum are precisely matched to the 120 ms delay for visual feedback to the circuit about behavioral errors. This specialization of the plasticity rules for the constraints of a particular circuit and learning task is acquired through experience. In dark-reared mice that never experienced visual feedback about oculomotor errors, synapses defaulted to a coincidence-based plasticity rule, with a corresponding delay in the timing of learned eye movements. This temporal metaplasticity persists into adulthood; when mice reared normally from birth were moved to dark housing as adults, the task-specific timing requirements for plasticity and the temporal accuracy of learning were lost and then re-established when visual experience was restored. Computational modeling suggests two general classes of biologically plausible mechanisms, each with multiple possible implementations, that can tune plasticity to distinct features of the statistics of neural activity. Temporal metaplasticity provides a potentially general mechanism for experience-dependent improvement in the way a circuit solves the "temporal credit assignment problem" inherent in most learning tasks, thereby providing a candidate synaptic mechanism for meta-learning.

neuroscience↗

bioRxiv2021

Restoration of BDNF-TrkB signaling rescues deficits in a mouse model of SCA6

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease resulting in motor coordination deficits and cerebellar pathology. Expression of brain-derived neurotrophic factor (BDNF) is reduced in several neurodegenerative diseases, including in post-mortem tissue from SCA6 patients. Here, we show that cerebellar BDNF levels are reduced at an early disease stage in a mouse model of SCA6 (SCA684Q/84Q). One month of voluntary exercise was sufficient to elevate BDNF expression, as well as rescue both motor coordination and cerebellar Purkinje cell firing rate deficits. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF) likewise improved motor coordination and reversed Purkinje cell firing rate deficits, suggesting that exercise acts via BDNF-TrkB signaling. Prolonged chronic 7,8-DHF administration rescued ataxia when treatment commenced near disease onset, but was ineffective when treatment was started late. These data suggest that 7,8-DHF, which is orally bioavailable and crosses the blood-brain barrier, is a promising therapeutic for SCA6 and argue for the importance of early intervention for SCA6.

neuroscience↗