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M P Stryker

Publications and source records attributed to M P Stryker.

At least 19 recordsLinked to original sources
PubMed2006

Sleep does not enhance the recovery of deprived eye responses in developing visual cortex.

Monocular deprivation (MD) during a critical period of visual development triggers a rapid remodeling of cortical responses in favor of the open eye. We have previously shown that this process is enhanced by sleep and is inhibited when the sleeping cortex is reversibly inactivated. A related but distinct form of cortical plasticity is evoked when the originally deprived eye (ODE) is reopened, and the non-deprived eye is closed during the critical period (reverse monocular deprivation (RMD)). Recent studies suggest that different mechanisms regulate the initial loss of deprived eye responses following MD and the recovery of deprived eye responses following RMD. In this study we investigated whether sleep also enhances RMD plasticity in critical period cats. Using polysomnography combined with microelectrode recordings and intrinsic signal optical imaging in visual cortex we show that sleep does not enhance the recovery of ODE responses following RMD. These findings add to the growing evidence that different forms of plasticity in vivo are regulated by distinct mechanisms and that sleep has divergent roles upon different types of experience-dependent cortical plasticity.

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PubMed2001

The CRE/CREB pathway is transiently expressed in thalamic circuit development and contributes to refinement of retinogeniculate axons.

The development of precise connections in the mammalian brain proceeds through refinement of initially diffuse patterns, a process that occurs largely within critical developmental windows. To elucidate the molecular pathways that orchestrate these early periods of circuit remodeling, we have examined the role of a calcium- and cAMP-regulated transcriptional pathway. We show that there is a window of CRE/CREB-mediated gene expression in the developing thalamus, which precedes neocortical expression. In the LGN, this wave of gene expression occurs prior to visual experience, but requires retinal function. Mutant mice with reduced CREB expression show loss of refinement of retinogeniculate projections. These results suggest an important role of the CRE/CREB transcriptional pathway in the coordination of experience-independent circuit remodeling during forebrain development.

Aging↗
PubMed2001

TrkB-like immunoreactivity is present on geniculocortical afferents in layer IV of kitten primary visual cortex.

Exogenous administration of the neurotrophins brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/5), or blockade of their endogenous actions, have been reported to affect the anatomic organization and physiological responses of neurons in developing mammalian primary visual cortex. Experimental alteration of levels of these neurotrophic factors can also influence the morphology of the geniculocortical afferents that project from the lateral geniculate nucleus (LGN) to primary visual cortex. BDNF and NT-4/5 are ligands of the TrkB tyrosine kinase receptor. Although multiple populations of cortical neurons express TrkB, it is not known whether geniculocortical afferents express this receptor on their axon branches in visual cortex. We have anatomically labeled geniculocortical afferents of postnatal day 40 kittens with the anterograde neuronal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and performed double-label immunofluorescence with a panel of anti-TrkB antibodies. Confocal microscopy and object-based colocalization analysis were used to measure levels of TrkB-like immunoreactivity (IR) on geniculocortical afferents in layer IV of primary visual cortex. By using a conservative analysis involving a comparison of measured colocalization with the amount of colocalization expected based on random overlap of TrkB puncta and PHA-L--labeled afferents, 3 of 5 anti-TrkB antibodies tested showed significant colocalization with the geniculocortical axons. Results for the other two antibodies were indeterminate. The indices obtained for colocalization of TrkB and geniculocortical afferents were also compared with the equivalent index obtained for GAD65, a protein that has a similar overall expression pattern to that of TrkB but is not expressed on geniculocortical axons. This analysis indicated that TrkB was present on geniculocortical axons for all five TrkB antibodies tested. TrkB-like IR was also observed on neuronal somata in the LGN. These results indicate that TrkB receptors on geniculocortical afferents are potential mediators of the actions of BDNF and NT-4/5 in developing visual cortex.

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PubMed2001

Rapid anatomical plasticity of horizontal connections in the developing visual cortex.

Experience can dramatically alter the responses of cortical neurons. During a critical period in the development of visual cortex, these changes are extremely rapid, taking place in 2 d or less. Anatomical substrates of these changes have long been sought, primarily in alterations in the principal visual input from the thalamus, but the significant changes that have been found take 1 week. Recent results indicate that the initial physiological changes in the cortical circuit take place outside of the primary input layer. We now find that rapid plasticity of binocular responses in the upper layers of cortex is mirrored by similarly rapid anatomical changes in the horizontal connections between ocular dominance columns in the upper layers, which reorganize within 2 d.

Aging↗
PubMed2001

Emergence of ocular dominance columns in cat visual cortex by 2 weeks of age.

Previous anatomic studies of the geniculocortical projection showed that ocular dominance columns emerge by 3 weeks of age in cat visual cortex, but recent optical imaging experiments have revealed a pattern of physiologic eye dominance by the end of the second week of life. We used two methods to search for an anatomic correlate of this early functional ocular dominance pattern. First, retrograde labeling of lateral geniculate nucleus (LGN) inputs to areas of cortex preferentially activated by one eye showed that the geniculocortical projection was already partially segregated by eye at postnatal day 14 (P14). Second, transneuronal label of geniculocortical afferents in flattened sections of cortex after a tracer injection into one eye showed a periodic pattern at P14 but not at P7. In the classic model for the development of ocular dominance columns, initially overlapping geniculocortical afferents segregate by means of an activity-dependent competitive process. Our data are consistent with this model but suggest that ocular dominance column formation begins between P7 and P14, approximately a week earlier than previously believed. The functional and anatomic data also reveal an early developmental bias toward contralateral eye afferents. This initial developmental bias is not consistent with a strictly Hebbian model for geniculocortical afferent segregation. The emergence of ocular dominance columns before the onset of the critical period for visual deprivation also suggests that the mechanisms for ocular dominance column formation may be partially distinct from those mediating plasticity later in life.

Aging↗
PubMed2001

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development.

Intracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the effects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF affects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no effect on the normal developmental segregation of geniculocortical afferents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-unit electrophysiology. Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active, producing an increase in the number of NGF-, TrkA-, p75(NTR)-, and choline acetyltransferase-positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons. We conclude that NGF delivered locally to axon terminals of cholinergic basal forebrain neurons resulted in increases in protein expression at the cell body through retrograde signaling.

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PubMed2001

Sleep enhances plasticity in the developing visual cortex.

During a critical period of brain development, occluding the vision of one eye causes a rapid remodeling of the visual cortex and its inputs. Sleep has been linked to other processes thought to depend on synaptic remodeling, but a role for sleep in this form of cortical plasticity has not been demonstrated. We found that sleep enhanced the effects of a preceding period of monocular deprivation on visual cortical responses, but wakefulness in complete darkness did not do so. The enhancement of plasticity by sleep was at least as great as that produced by an equal amount of additional deprivation. These findings demonstrate that sleep and sleep loss modify experience-dependent cortical plasticity in vivo. They suggest that sleep in early life may play a crucial role in brain development.

Action Potentials↗
PubMed2000

Neurotrophin-4/5 alters responses and blocks the effect of monocular deprivation in cat visual cortex during the critical period.

The mechanisms underlying changes in neural responses and connections in the visual cortex may be studied by occluding one eye during a critical period in early postnatal life. Under these conditions, neurons in the visual cortex rapidly lose their responses to the deprived eye and ultimately lose many of their inputs from that eye. Cats at the peak of the critical period received infusions of exogenous neurotrophin NT-4/5 into primary visual cortex beginning before a short period of monocular deprivation. Within areas affected by NT-4/5, cortical cells remained responsive to the deprived eye, and maps of ocular dominance were no longer evident using intrinsic-signal optical imaging. Cortical cells also became broadly tuned for stimulus orientation and less responsive to visual stimulation through either eye. These effects required at least 48 hr exposure to the neurotrophin and were specific for trkB, because they were not seen with the trkA or trkC ligands NGF or NT-3. Even after neurons had already lost their responses to the deprived eye, subsequent NT-4/5 infusion could restore them. The NT-4/5 effects were not seen after the critical period. Together, these results suggest that trkB activation during the critical period may promote promiscuous connections independent of correlated activity.

Aging↗
PubMed2000

Spatial frequency maps in cat visual cortex.

Neurons in the primary visual cortex (V1) respond preferentially to stimuli with distinct orientations and spatial frequencies. Although the organization of orientation selectivity has been thoroughly described, the arrangement of spatial frequency (SF) preference in V1 is controversial. Several layouts have been suggested, including laminar, columnar, clustered, pinwheel, and binary (high and low SF domains). We have reexamined the cortical organization of SF preference by imaging intrinsic cortical signals induced by stimuli of various orientations and SFs. SF preference maps, produced from optimally oriented stimuli, were verified using targeted microelectrode recordings. We found that a wide range of SFs is represented independently and mostly continuously within V1. Domains with SF preferences at the extremes of the SF continuum were separated by no more than (3/4) mm (conforming to the hypercolumn description of cortical organization) and were often found at pinwheel center singularities in the cortical map of orientation preference. The organization of cortical maps permits nearly all combinations of orientation and SF preference to be represented in V1, and the overall arrangement of SF preference in V1 suggests that SF-specific adaptation effects, found in psychophysical experiments, may be explained by local interactions within a given SF domain. By reanalyzing our data using a different definition of SF preference than is used in electrophysiological and psychophysical studies, we can reproduce the different SF organizations suggested by earlier studies.

Algorithms↗
PubMed2000

Distributions of synaptic vesicle proteins and GAD65 in deprived and nondeprived ocular dominance columns in layer IV of kitten primary visual cortex are unaffected by monocular deprivation.

Two days of monocular deprivation (MD) of kittens during a critical period of development is known to produce a loss of visual responses in the primary visual cortex to stimulation of the nondeprived eye, and 7 days of deprivation results in retraction of axon branches and loss of presynaptic sites from deprived-eye geniculocortical arbors. The rapid loss of responsiveness to deprived-eye visual stimulation could be due to a decrease in intracortical excitatory input to deprived-eye ocular dominance columns (ODCs) relative to nondeprived-eye columns. Alternatively, deprived-eye visual responses could be suppressed by an increase in intracortical inhibition in deprived columns relative to nondeprived columns. We tested these hypotheses in critical period kittens by labeling ODCs in layer IV of primary visual cortex with injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into lamina A of the lateral geniculate nucleus (LGN). After either 2 or 7 days of MD, densities of intracortical excitatory presynaptic sites within deprived relative to nondeprived ODCs were estimated by measuring synaptic vesicle protein (SVP) immunoreactivity (IR). Because most of the synapses within layer IV of primary visual cortex are excitatory inputs from other cortical neurons, levels of SVP-IR provide an estimate of the amount of intracortical excitatory input. We also measured levels of immunoreactivity of the inhibitory presynaptic terminal marker glutamic acid decarboxylase (GAD)65 in deprived relative to nondeprived ODCs. Monocular deprivation (either 2 or 7 days) had no effect on the distributions of either SVP- or GAD65-IR in deprived and nondeprived columns. Therefore, the rapid loss of deprived-eye visual responsiveness following MD is due neither to a decrease in intracortical excitatory presynaptic sites nor to an increase in intracortical inhibitory presynaptic sites in layer IV of deprived-eye ODCs relative to nondeprived columns.

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PubMed2000

Rapid extragranular plasticity in the absence of thalamocortical plasticity in the developing primary visual cortex.

Monocular deprivation during early postnatal development remodels the circuitry of the primary visual cortex so that most neurons respond poorly to stimuli presented to the deprived eye. This rapid physiological change is ultimately accompanied by a matching anatomical loss of input from the deprived eye. This remodeling is thought to be initiated at the thalamocortical synapse. Ocular dominance plasticity after brief (24 hours) monocular deprivation was analyzed by intrinsic signal optical imaging and by targeted extracellular unit recordings. Deprived-eye responsiveness was lost in the extragranular layers, whereas normal binocularity in layer IV was preserved. This finding supports the hypothesis that thalamocortical organization is guided by earlier changes at higher stages.

Animals↗
PubMed2000

A method for measuring colocalization of presynaptic markers with anatomically labeled axons using double label immunofluorescence and confocal microscopy.

Information concerning the location and distribution of presynaptic neurotransmitter release sites within anatomically labeled axons would be of value for a large number of studies in functional anatomy, development, and plasticity. Here we report a method for localizing presynaptic sites within identified arbors of interest using anterograde anatomical tracer injections to label axonal projections and synaptic vesicle protein (SVP) antibodies to label presumptive presynaptic terminals. The axons and presynaptic sites are independently visualized with double label immunofluorescence and confocal microscopy. Stacks of images representing adjacent focal planes are collected, and image processing techniques are applied to identify the location of each axonal branch segment and each cluster of SVP label in three-dimensional space. Segmentation of the SVP label into distinct pixel clusters in three-dimensional space, followed by colocalization of these clusters with the labeled axons (object-based analysis), yields much more reliable and sensitive measures of colocalization than a simple determination of the number (or summed intensities) of colocalized pixels in a single optical section (pixel-based analysis). The method has been extended to measure the colocalization of antigens that are not located at the presynaptic terminal with a labeled population of axons.

Animals↗
PubMed2000

Cortical degeneration in the absence of neurotrophin signaling: dendritic retraction and neuronal loss after removal of the receptor TrkB.

To examine functions of TrkB in the adult CNS, TrkB has been removed from neurons expressing CaMKII, primarily pyramidal neurons, using Cre-mediated recombination. A floxed trkB allele was designed so that neurons lacking TrkB express tau-beta-galactosidase. Following trkB deletion in pyramidal cells, their dendritic arbors are altered, and cortical layers II/III and V are compressed, after which there is an apparent loss of mutant neurons expressing the transcription factor SCIP but not of those expressing Otx-1. Loss of neurons expressing SCIP requires deletion of trkB within affected neurons; reduction of neuronal ER81 expression does not, suggesting both direct and indirect effects of TrkB loss. Thus, TrkB is required for the maintenance of specific populations of cells in the adult neocortex.

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PubMed1999

Synaptic density in geniculocortical afferents remains constant after monocular deprivation in the cat.

Monocular eyelid closure in cats during a critical period in development produces both physiological plasticity, as indicated by a loss of responsiveness of primary visual cortical neurons to deprived eye stimulation, and morphological plasticity, as demonstrated by a decrease in the total length of individual geniculocortical arbors representing the deprived eye. Although the physiological plasticity appears maximal after 2 d of monocular deprivation (MD), the shrinkage of deprived-eye geniculocortical arbors is less than half-maximal at 4 d and is not maximal until 7 d of deprivation, at which time the deprived arbors are approximately half their previous size. To study this form of plasticity at the level of individual thalamocortical synapses rather than arbors, we developed a new double-label colocalization technique. First, geniculocortical afferent arbors serving either the deprived or nondeprived eye were labeled by injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin into lamina A of the lateral geniculate nucleus. Then, using antibodies to synaptic vesicle proteins, we identified presynaptic terminals within the labeled arbors in layer IV of the primary visual cortex. Analysis of serial optical sections obtained using confocal microscopy allowed measurement of the numerical density of presynaptic sites and the relative amounts of synaptic vesicle protein in geniculocortical afferents after both 2 and 7 d of MD. We found that the density of synapses in geniculocortical axons was similar for deprived and nondeprived afferents, suggesting that this feature of the afferents is conserved even during periods in which synapse number is reduced by half in deprived-eye arbors. These results are not consistent with the hypothesis that a rapid loss of deprived-eye geniculocortical presynaptic sites is responsible for the prompt physiological effects of MD.

Aging↗
PubMed1999

Brain-derived neurotrophic factor overexpression induces precocious critical period in mouse visual cortex.

Brain-derived neurotrophic factor (BDNF) is a candidate molecule for regulating activity-dependent synaptic plasticity on the grounds of its expression pattern in developing visual cortex and that of its receptor, trkB (Castr¿n et al., 1992; Bozzi et al., 1995; Schoups et al., 1995; Cabelli et al., 1996), as well as the modulation of these patterns by activity (Castr¿n et al., 1992; Bozzi et al., 1995; Schoups et al., 1995). Infusing trkB ligands or their neutralizing agents, the trkB-IgG fusion proteins, into visual cortex alters the development and plasticity of ocular dominance columns (Cabelli et al., 1995; Riddle et al., 1995; Galuske et al., 1996 ; Gillespie et al., 1996; Cabelli et al., 1997). To test further the physiological role of BDNF, we studied a transgenic mouse that expresses elevated levels of BDNF in primary visual cortex (V1) postnatally (Huang et al., 1999). We found that unlike the infusion experiments, excess BDNF expressed in mouse visual cortex did not block ocular dominance plasticity. Instead, single neurons in V1 of the BDNF transgenic mice were as susceptible to the effects of monocular deprivation (MD) as neurons in wild-type mice, but only during a precocious critical period. At a time when V1 in the wild-type mouse responded maximally to a 4 d MD with a reduction in its response to deprived eye visual stimulation, the transgenic mouse V1 had already passed the peak of its precocious critical period and no longer responded maximally. This finding suggests a role for BDNF in promoting the postnatal maturation of cortical circuitry.

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