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

Abstract

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.

Long-Distance Retrograde Effects of Botulinum Neurotoxin A

“…BoNT/Etruncated SNAP-25 was restricted to the injected hemisphere at all time points examined ( Fig. 2C), in keeping with our previous reports (Costantin et al, 2005;Antonucci et al, 2007;Caleo et al, 2007). In animals treated with BoNT/A, proteolysis of SNAP-25 was confined to the ipsilateral hippocampus 1 d after toxin administration.…”

“…BoNT/A and BoNT/E were prepared and tested as described previously (Schiavo and Montecucco, 1995;Costantin et al, 2005;Caleo et al, 2007). Intrahippocampal injections (0.2 l of a 10 nM solution; BoNT/A, n ϭ 48 mice, BoNT/E, n ϭ 27 mice) were performed with a glass micropipette connected to an injector.…”

“…The antibody against BoNT/E-truncated SNAP-25 has been characterized previously (Costantin et al, 2005; Antonucci et al, 2007; Caleo et al, 2007). Here, a dose-response curve was done to determine the sensitivity of the anti-BoNT/A-cleaved SNAP-25 antibody and to establish how levels of cleaved SNAP-25 relate to the amounts of injected toxin.…”

Insights into Visual Cortex Plasticity: Interaction Between Genes and Sensory Experience

“…Transient blockade of synaptic activity arrested maturation of visual acuity not only in the treated, but also in the contralateral hemisphere (Caleo et al, 2007). The CP for plasticity was also extended in both hemispheres (Caleo et al, 2007). These findings indicate that maturation of the blocked cortex is superimposable to that of the opposite side.…”

“…A crucial role for callosal input activity in the functional maturation of the VC was indicated by experiments in which activity was unilaterally blocked in the striate cortex during the CP. Transient blockade of synaptic activity arrested maturation of visual acuity not only in the treated, but also in the contralateral hemisphere (Caleo et al, 2007). The CP for plasticity was also extended in both hemispheres (Caleo et al, 2007).…”