Carla Shatz "Releasing the Brake on Ocular Dominance Plasticity"
Carla Shartz: Releasing the Brake on Ocular Dominance Plasticity.
Vision Sciences Society Annual Meeting, Keynote 2010.
Connections in adult visual system are highly precise, but they do not start out that way. Precision emerges during critical periods of development as synaptic connections remodel, a process requiring neural activity and involving regression of some synapses and strengthening and stabilization of others. Activity also regulates neuronal genes; in an unbiased PCR-based differential screen, we discovered unexpectedly that MHC Class I genes are expressed in neurons and are regulated by spontaneous activity and visual experience (Corriveau et al, 1998; Goddard et al, 2007).
To assess requirements for MHCI in the CNS, mice lacking expression of specific MHCI genes were examined. Synapse regression in developing visual system did not occur, synaptic strengthening was greater than normal in adult hippocampus, and ocular dominance (OD) plasticity in visual cortex was enhanced (Huh et al, 2000; Datwani et al, 2009). We searched for receptors that could interact with neuronal MHCI and carry out these activity-dependent processes. mRNA for PirB, an innate immune receptor, was found highly expressed in neurons in many regions of mouse CNS. We generated mutant mice lacking PirB function and discovered that OD plasticity is also enhanced (Syken et al., 2006), as is hippocampal LTP. Thus, MHCI ligands signaling via PirB receptor may function to “brake” activity- dependent synaptic plasticity. Together, results imply that these molecules, thought previously to function only in the immune system, may also act at neuronal synapses to limit how much- or perhaps how quickly- synapse strength changes in response to new experience. These molecules may be crucial for controlling circuit excitability and stability in developing as well as adult brain, and changes in their function may contribute to developmental disorders such as Autism, Dyslexia and even Schizophrenia.
Supported by NIH Grants EY02858, MH071666, the Mathers Charitable Foundation and the Dana Foundation.
Vision Sciences Society Annual Meeting, Keynote 2010.
Connections in adult visual system are highly precise, but they do not start out that way. Precision emerges during critical periods of development as synaptic connections remodel, a process requiring neural activity and involving regression of some synapses and strengthening and stabilization of others. Activity also regulates neuronal genes; in an unbiased PCR-based differential screen, we discovered unexpectedly that MHC Class I genes are expressed in neurons and are regulated by spontaneous activity and visual experience (Corriveau et al, 1998; Goddard et al, 2007).
To assess requirements for MHCI in the CNS, mice lacking expression of specific MHCI genes were examined. Synapse regression in developing visual system did not occur, synaptic strengthening was greater than normal in adult hippocampus, and ocular dominance (OD) plasticity in visual cortex was enhanced (Huh et al, 2000; Datwani et al, 2009). We searched for receptors that could interact with neuronal MHCI and carry out these activity-dependent processes. mRNA for PirB, an innate immune receptor, was found highly expressed in neurons in many regions of mouse CNS. We generated mutant mice lacking PirB function and discovered that OD plasticity is also enhanced (Syken et al., 2006), as is hippocampal LTP. Thus, MHCI ligands signaling via PirB receptor may function to “brake” activity- dependent synaptic plasticity. Together, results imply that these molecules, thought previously to function only in the immune system, may also act at neuronal synapses to limit how much- or perhaps how quickly- synapse strength changes in response to new experience. These molecules may be crucial for controlling circuit excitability and stability in developing as well as adult brain, and changes in their function may contribute to developmental disorders such as Autism, Dyslexia and even Schizophrenia.
Supported by NIH Grants EY02858, MH071666, the Mathers Charitable Foundation and the Dana Foundation.