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Peter C Kind

Publications and source records attributed to Peter C Kind.

9 recordsLinked to original sources
PubMed2006

Involvement of protein kinase A in patterning of the mouse somatosensory cortex.

Patterning of the mouse somatosensory cortex is unusually evident because of the presence of a "barrel field." Presynaptic serotonin and postsynaptic glutamate receptors regulate barrel formation, but little is known of the intracellular signaling pathways through which they act. To determine whether protein kinase A (PKA) plays a role in the development of the barrel field, we examined five viable PKA subunit-specific knock-out (KO) mouse lines for barrel field abnormalities. Barrels are present in these mice, but those lacking the RIIbeta subunit display significantly reduced contrast between the cell densities of barrel hollows and sides compared with wild-type animals. Thalamocortical afferent segregation in the posterior medial barrel subfield appeared normal, suggesting a postsynaptic site of gene action for the RIIbeta protein. Immunoelectron microscopy confirmed that RIIbeta was selectively localized to dendrites and dendritic spines. Mice lacking RIIbeta show reduced glutamate receptor A (GluRA) subunit insertion into the postsynaptic density in postnatal day 7 somatosensory cortex; however, GluRA KO mice developed normal barrels. Our results clearly demonstrate a role for postsynaptic PKA signaling pathways in barrel differentiation. They also demonstrate a clear dissociation between the regulation of GluRA trafficking by PKA and its role in barrel formation. Finally, although a role for PKA downstream of cAMP cannot be ruled out, these data suggest that PKA may not be the principle downstream target because none of the mutants showed a barrelless phenotype similar to that observed in adenylate cyclase type 1 KO mice. These results give insight into activity-dependent mechanisms that regulate barrel formation.

Animals↗
PubMed2006

Synaptic Ras GTPase activating protein regulates pattern formation in the trigeminal system of mice.

The development of ordered connections or "maps" within the nervous system is a common feature of sensory systems and is crucial for their normal function. NMDA receptors are known to play a key role in the formation of these maps; however, the intracellular signaling pathways that mediate the effects of glutamate are poorly understood. Here, we demonstrate that SynGAP, a synaptic Ras GTPase activating protein, is essential for the anatomical development of whisker-related patterns in the developing somatosensory pathways in rodent forebrain. Mice lacking SynGAP show only partial segregation of barreloids in the thalamus, and thalamocortical axons segregate into rows but do not form whisker-related patches. In cortex, layer 4 cells do not aggregate to form barrels. In Syngap(+/-) animals, barreloids develop normally, and thalamocortical afferents segregate in layer 4, but cell segregation is retarded. SynGAP is not necessary for the development of whisker-related patterns in the brainstem. Immunoelectron microscopy for SynGAP from layer 4 revealed a postsynaptic localization with labeling in developing postsynaptic densities (PSDs). Biochemically, SynGAP associates with the PSD in a PSD-95-independent manner, and Psd-95(-/-) animals develop normal barrels. These data demonstrate an essential role for SynGAP signaling in the activity-dependent development of whisker-related maps selectively in forebrain structures indicating that the intracellular pathways by which NMDA receptor activation mediates map formation differ between brain regions and developmental stage.

Animals↗
PubMed2006

Short periods of concordant binocular vision prevent the development of deprivation amblyopia.

Based in part on deprivation studies, it is generally agreed that the development of vision and of the central visual pathways of higher mammals such as cats and primates is experience-dependent. Past deprivation experiments employed periods of exclusively abnormal early visual input. Because of the absence of any normal visual input, such studies indicate only the extremes to which the visual system can change in response to visually driven activity (i.e. its capabilities) rather than provide insight into the role of early visual input in normal development (i.e. what it actually does). We examined the possibility that certain visual input, i.e. normal concordant binocular vision, may be more efficacious than others with respect to its effects on the developing visual system and on vision. On a daily basis, one type of visual input, i.e. normal binocular experience (BE), was pitted against abnormal (monocular exposure, ME) input in order to see if one was more effective. We show that 2 h of daily normal concordant, but not discordant, BE outweighs or protects against as much as 5 h of daily abnormal input to permit the development of normal grating acuity and alignment accuracy in the two eyes. Further, we show that splitting the period of BE into two 1-h periods straddling the period of ME was ineffective, thereby indicating the 2 h of BE each day must be continuous to protect against the development of amblyopia.

Adaptation, Physiological↗
PubMed2005

Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signalling.

The phospholipase C-beta1 (PLC-beta1) signalling pathway, activated via metabotropic glutamate receptors (mGluRs), is implicated in activity-dependent development of the cerebral cortex, as both PLC-beta1 and mGluR5 knockout mice exhibit disrupted barrel formation in somatosensory cortex. To characterize the effects of this signalling system on development of synaptic circuitry in barrel cortex, we have examined neuronal ultrastructure, synapse formation and dendritic spine morphology in PLC-beta1 knockout mice. Qualitative ultrastructure of neurons and synapse density in layers 2-4 of barrel cortex were unchanged in PLC-beta1 knockout mice during development [postnatal day (P) 5] and in mature cortex (P19-21). We found a decrease in the proportion of synapses with symmetric morphology at P5 that was gone by P19-21, indicating a transient imbalance in excitatory and inhibitory circuitry. We also investigated dendritic spines by back-labelling layer 5 pyramidal neurons with carbocyanine. We observed normal dendritic spine densities on apical dendrites as they passed through layer 4 of barrel cortex, but spine morphology was altered in PLC-beta1 knockout mice at P9. These observations indicate that the PLC-beta1 signalling pathway plays a role in the development of normal cortical circuitry. Interrupting this regulation leads to changes in synapse and dendritic spine morphology, possibly altering post-synaptic integration of signal.

Algorithms↗
PubMed2005

Differential expression of two NMDA receptor interacting proteins, PSD-95 and SynGAP during mouse development.

Patterns of neural activity mediated by N-methyl-D-aspartate (NMDA) receptors are known to play important roles in development of the central nervous system. However, the signalling pathways downstream from NMDA receptors that are critical for normal neuronal development are not yet clearly understood. NMDA receptors interact with various signalling proteins via scaffolding proteins, which are important in adult neuronal and behavioural plasticity. For example, the NR2B subunits of the NMDA receptor interact with postsynaptic density 95 (PSD-95), which in turn binds to synaptic ras GTPase-activating protein (SynGAP). Interestingly, the developmental phenotype of mice carrying null mutations in these genes differ. NR2B and SynGAP homozygote mice die within the first week of birth whereas PSD-95 homozygote mice survive to adulthood. We therefore examined the expression patterns of PSD-95 and SynGAP genes from embryonic stages to adult using lacZ (beta-galactosidase) marker gene knock-in mice. Dramatic changes of expression were observed throughout development in brain and other tissues. Although SynGAP binds PSD-95, both genes had distinct, as well as overlapping expression. SynGAP expression peaked at times of synaptogenesis and developmental plasticity in contrast to PSD-95, which was expressed throughout the brain from early embryonic stages. Furthermore, SynGAP showed a more spatially restricted pattern as illustrated by its restriction to forebrain in contrast to PSD-95, which was also found in mid- and hindbrain. These data support the model that synaptic signalling complexes are heterogeneous and individual components show temporal and spatial specificity during development.

Animals↗
PubMed2003

Brief daily periods of binocular vision prevent deprivation-induced acuity loss.

The role of experience in the development of the central visual pathways has been explored in the past through examination of the consequences of imposed periods of continuously abnormal or biased visual input. The massive changes in the visual cortex (area 17) induced by selected early visual experience, especially monocular deprivation (MD) or experience (ME) where patterned visual input is provided to just one eye, are accompanied by profound and long-standing visual deficits. Although the use of exclusively abnormal experience permits identification of those aspects of the visual cortex and of visual function that can be influenced by visual experience during development, this approach may provide a distorted view of the nature of the role of visual experience because of the absence of any normal visual input. In this study a different approach was used whereby animals were provided daily with separate periods of normal (i.e., binocular exposure) and abnormal (monocular exposure) visual experience. We show that 2 hr of daily normal concordant binocular experience (BE) can outweigh or protect against much longer periods of monocular deprivation (MD) and permit the development of normal visual acuities in the two eyes. This result is not what would be expected if all visual input had equal influence on visual development.

Animals↗
PubMed2002

The role of activity in development of the visual system.

Neuronal activity is important for both the initial formation and the subsequent refinement of anatomical and physiological features of the mammalian visual system. Here we examine recent evidence concerning the role that spontaneous activity plays in axonal segregation, both of retinogeniculate afferents into eye-specific layers and of geniculocortical afferents into ocular dominance bands. We also assess the role of activity in the generation and plasticity of orientation selectivity in the primary visual cortex. Finally, we review recent challenges to textbook views on how inputs representing the two eyes interact during the critical period of visual cortical plasticity.

Aging↗
PubMed2002

Correlated binocular activity guides recovery from monocular deprivation.

Monocular deprivation (MD) has much more rapid and severe effects on the ocular dominance of neurons in the primary visual cortex (V1) than does binocular deprivation. This finding underlies the widely held hypothesis that the developmental plasticity of ocular dominance reflects competitive interactions for synaptic space between inputs from the two eyes. According to this view, the relative levels of evoked activity in afferents representing the two eyes determine functional changes in response to altered visual experience. However, if the deprived eye of a monocularly deprived kitten is simply reopened, there is substantial physiological and behavioural recovery, leading to the suggestion that absolute activity levels, or some other non-competitive mechanisms, determine the degree of recovery from MD. Here we provide evidence that correlated binocular input is essential for such recovery. Recovery is far less complete if the two eyes are misaligned after a period of MD. This is a powerful demonstration of the importance of cooperative, associative mechanisms in the developing visual cortex.

Animals↗