Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity

Matteo Caleo,1* Laura Restani,2* Laura Gianfranceschi,2* Laura Costantin,2 Chiara Rossi,1 Ornella Rossetto,3
Cesare Montecucco,3 and Lamberto Maffei1,2
1Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche and 2Scuola Normale Superiore, 56100 Pisa, Italy, and 3Dipartimento di Scienze Biomediche, Universita` di Padova, 35121 Padova, Italy

Neural circuits in the cerebral cortex are shaped by experience during “critical periods” early in life. For example, visual cortex is immature at the time of eye opening and gradually develops its functional properties during a sensitive period. Very few reports have addressed the role of intrinsic neural activity in cortical maturation. Here we have exploited the bacterial enzyme botulinum neurotoxin E (BoNT/E) to produce a unilateral, reversible blockade of neural activity in rat visual cortex during the sensitive period. BoNT/E is a highly selective protease that interferes with transmitter release via cleavage of the synaptic protein SNAP-25 (synaptosomal-associated protein of 25 kDa). Unilateral, intracortical injections of BoNT/E were made at the time of eye opening and resulted in the silencing of the
treated, but not contralateral, hemisphere for a period of 2 weeks. We found that visual acuity was permanently reduced in the blocked hemisphere, and the critical period for ocular dominance plasticity persisted into adulthood. Unexpectedly, these effects extended equally to the contralateral, uninjected side, demonstrating a fundamental role for interhemispheric connections in cortical maturation.

Key words: botulinum neurotoxin; synaptic transmission; critical period; visual acuity; monocular deprivation; corpus callosum

(Fonte: The Journal of Neuroscience, 25 Aprile 2007)

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