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Tommaso Pizzorusso

Publications and source records attributed to Tommaso Pizzorusso.

9 recordsLinked to original sources
PubMed2006

Structural and functional recovery from early monocular deprivation in adult rats.

Visual deficits caused by abnormal visual experience during development are hard to recover in adult animals. Removal of chondroitin sulfate proteoglycans from the mature extracellular matrix with chondroitinase ABC promotes plasticity in the adult visual cortex. We tested whether chondroitinase ABC treatment of adult rats facilitates anatomical, functional, and behavioral recovery from the effects of a period of monocular deprivation initiated during the critical period for monocular deprivation. We found that chondroitinase ABC treatment coupled with reverse lid-suturing causes a complete recovery of ocular dominance, visual acuity, and dendritic spine density in adult rats. Thus, manipulations of the extracellular matrix can be used to promote functional recovery in the adult cortex.

Aging↗
PubMed2004

Extracellular matrix and visual cortical plasticity: freeing the synapse.

The effects of monocular deprivation (MD) on the ocular dominance of visual cortical neurons are a paradigmatic example of experience-dependent plasticity. Here we review recent data showing that extracellular matrix (ECM) plays an important role in the control of experience-dependent plasticity both in the developing and adult visual cortex.

Animals↗
PubMed2004

A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.

Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels. We generated a knockin mouse model carrying the human pure FHM-1 R192Q mutation and found multiple gain-of-function effects. These include increased Ca(v)2.1 current density in cerebellar neurons, enhanced neurotransmission at the neuromuscular junction, and, in the intact animal, a reduced threshold and increased velocity of cortical spreading depression (CSD; the likely mechanism for the migraine aura). Our data show that the increased susceptibility for CSD and aura in migraine may be due to cortical hyperexcitability. The R192Q FHM-1 mouse is a promising animal model to study migraine mechanisms and treatments.

Animals↗
PubMed2003

Patterned vision causes CRE-mediated gene expression in the visual cortex through PKA and ERK.

Normal visual experience during postnatal development is necessary for the maturation of visual cortical circuits and acts through molecular mechanisms that are still poorly understood. Recently, it has been shown that ERK (extracellular signal-regulated kinase) 1/2, protein kinase A (PKA), and CREB (cAMP response element-binding protein) are crucial factors for experience-dependent development of the visual cortex, but very little is known about the role of visual experience in their activation. Here, we show that visual stimulation after a brief period of dark rearing caused a transient ERK activation in the visual cortex. Visually induced ERK activation occurred primarily in excitatory neurons of layers II-III and VI and was prevented by binocular lid suture. ERK phosphorylation was strongly reduced by cortical infusion with the cAMP-PKA inhibitor Rp-8-Cl-cAMPS, thus establishing a link between PKA and ERK activation. To analyze the downstream consequences of ERK and PKA signaling, we studied the action of visual stimulation on transcription of genes controlled by CREB in transgenic mice carrying the LacZ reporter gene under the control of the CRE (cAMP response element) promoter. Visual stimulation triggered a prolonged episode of CRE-mediated gene expression in the visual cortex that was suppressed by infusion with the ERK inhibitor U0126. Cortical administration of Rp-8-Cl-cAMPS attenuated the experience-dependent activation of CRE-mediated gene transcription. These results show that ERK phosphorylation in visual cortical neurons represents a molecular readout of patterned visual stimuli and that visual activation of ERK involves the cAMP-PKA system. Finally, because CRE-mediated gene expression was totally dependent on ERK activation, we suggest that PKA action on CRE-mediated gene expression is mediated by ERK.

Anesthetics, Intravenous↗
PubMed2003

Molecular basis of plasticity in the visual cortex.

Sensory experience is known to shape the maturation of cortical circuits during development. A paradigmatic example is the effect of monocular deprivation on ocular dominance of visual cortical neurons. Although visual cortical plasticity has been widely studied since its initial discovery by Hubel and Wiesel >40 years ago, the description of the underlying molecular mechanisms has lagged behind. Several new findings are now beginning to close this gap. Recent data deepen our knowledge of the factors involved in the intercellular communication and intracellular signaling that mediate experience-dependent plasticity in the developing visual cortex. In addition, new findings suggest a role for the extracellular matrix in inhibition of ocular-dominance plasticity in the adult visual cortex.

Animals↗
PubMed2002

Heterozygous knock-out mice for brain-derived neurotrophic factor show a pathway-specific impairment of long-term potentiation but normal critical period for monocular deprivation.

Genetic deletion of a single allele of the BDNF gene affects hippocampal LTP and causes several behavioral phenotypes, including deficits in spatial learning. In the developing visual cortex, overexpression of BDNF accelerates the time course of the critical period for monocular deprivation (MD), and exogenous administration of BDNF alters the outcome of MD. We asked whether reduced levels of BDNF could affect visual cortex plasticity by studying long-term potentiation (LTP) induction and the effects of MD in heterozygous BDNF knock-out mice. We found that theta burst stimulation that induced LTP in the layer IV-III pathway of wild-type (wt) mice caused only a transient potentiation in BDNF+/- mice, and that this potentiation vanished in 25 min. In contrast, LTP elicited by stimulation of the white matter (WM), a form of LTP that can be induced only during the critical period, occurred normally in wt and BDNF+/- mice. The effects of MD during the critical period were similar in wt and BDNF+/- mice, indicating that layer IV-evoked, layer III LTP is not required for ocular dominance plasticity. We then asked whether reduction of cortical BDNF levels could prolong the critical period for MD and for the WM-evoked, layer III LTP induction. We found that in adult BDNF+/- mice, WM-evoked, layer III LTP was not inducible, and that the critical period for MD terminated normally. We conclude that deletion of one copy of the BDNF gene selectively impairs LTP of the layer IV-III pathway but does not alter ocular dominance plasticity.

Animals↗
PubMed2002

Reactivation of ocular dominance plasticity in the adult visual cortex.

In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.

Animals↗
PubMed2002

Electrophysiology of the postreceptoral visual pathway in mice.

Pattern VEPs have been recorded locally from the binocular portion of the primary visual cortex of wild type- and different transgenic mice by means of microelectrodes. Local pattern VEPs have been used on the one hand to obtain information on basic cortical layout (topography, laminar analysis) and ocularity (relative contribution of the contralateral and ipsilateral eye), and on the other hand to evaluate several aspects of visual physiology that have a counterpart in visual behavior (visual acuity, contrast sensitivity, motion sensitivity, response latency). As compared to visual behavior, pattern VEPs offer the advantage that several aspects of vision can be evaluated in the same animals, including those with poor behavior due to motor- or cognitive deficits, even during the postnatal development. Pattern VEPs provide a means for characterizing the visual phenotype of mutant mice and for the evaluation of the effects induced by experimental manipulation.

Animals↗