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Small modulation of ongoing cortical dynamics by sensory input during natural vision.

During vision, it is believed that neural activity in the primary visual cortex is predominantly driven by sensory input from the environment. However, visual cortical neurons respond to repeated presentations of the same stimulus with a high degree of variability. Although this variability has been considered to be noise owing to random spontaneous activity within the cortex, recent studies show that spontaneous activity has a highly coherent spatio-temporal structure. This raises the possibility that the pattern of this spontaneous activity may shape neural responses during natural viewing conditions to a larger extent than previously thought. Here, we examine the relationship between spontaneous activity and the response of primary visual cortical neurons to dynamic natural-scene and random-noise film images in awake, freely viewing ferrets from the time of eye opening to maturity. The correspondence between evoked neural activity and the structure of the input signal was weak in young animals, but systematically improved with age. This improvement was linked to a shift in the dynamics of spontaneous activity. At all ages including the mature animal, correlations in spontaneous neural firing were only slightly modified by visual stimulation, irrespective of the sensory input. These results suggest that in both the developing and mature visual cortex, sensory evoked neural activity represents the modulation and triggering of ongoing circuit dynamics by input signals, rather than directly reflecting the structure of the input signal itself.

Action Potentials↗

Critical period mechanisms in developing visual cortex.

Binocular vision is shaped by experience during a critical period of early postnatal life. Loss of visual acuity following monocular deprivation is mediated by a shift of spiking output from the primary visual cortex. Both synaptic and network explanations have been offered for this heightened brain plasticity. Direct experimental control over its timing, duration, and closure has now been achieved through a consideration of balanced local circuit excitation-inhibition. Notably, canonical models of homosynaptic plasticity at excitatory synapses alone (LTP/LTD) fail to produce predictable manipulations of the critical period in vivo. Instead, a late functional maturation of intracortical inhibition is the driving force, with one subtype in particular standing out. Parvalbumin-positive large basket cells that innervate target cell bodies with synapses containing the alpha1-subunit of GABA(A) receptors appear to be critical. With age, these cells are preferentially enwrapped in peri-neuronal nets of extracellular matrix molecules, whose disruption by chondroitinase treatment reactivates ocular dominance plasticity in adulthood. In fact, critical period plasticity is best viewed as a continuum of local circuit computations ending in structural consolidation of inputs. Monocular deprivation induces an increase of endogenous proteolytic (tPA-plasmin) activity and consequently motility of spines followed by their pruning, then re-growth. These early morphological events faithfully reflect competition only during the critical period and lie downstream of excitatory-inhibitory balance on a timescale (of days) consistent with the physiological loss of deprived-eye responses in vivo. Ultimately, thalamic afferents retract or expand accordingly to hardwire the rapid functional changes in connectivity. Competition detected by local inhibitory circuits then implemented at an extracellular locus by proteases represents a novel, cellular understanding of the critical period mechanism. It is hoped that this paradigm shift will lead to novel therapies and training strategies for rehabilitation, recovery from injury, and lifelong learning in adulthood.

Animals↗

An oscillation-based model for the neuronal basis of attention.

We propose a model for the neuronal implementation of selective visual attention based on the temporal structure of neuronal activity. In particular, we set out to explain the electrophysiological data from areas V4 and IT in monkey cortex of Moran and Desimone [(1985) Science, 229, 782-784] using the "temporal tagging" hypothesis of Crick and Koch [(1990a) Cold Spring Harbor Symposiums in Quantitative Biology, LV, 953-962; (1990b) Seminars in the neurosciences (pp. 1-36)]. Neurons in primary visual cortex respond to visual stimuli with a Poisson distributed spike train with an appropriate, stimulus-dependent mean firing rate. The firing rate of neurons whose receptive fields overlap with the "focus of attention" is modulated with a periodic function in the 40 Hz range, such that their mean firing rate is identical to the mean firing rate of neurons in "non-attended" areas. This modulation is detected by inhibitory interneurons in V4 and is used to suppress the response of V4 cells associated with non-attended visual stimuli. Using very simple single-cell models, we obtain quantitative agreement with Moran and Desimone's (1985) experiments.

Action Potentials↗

Preliminary data on the metabolic brain pattern of patients with winter seasonal affective disorder.

The brain metabolic pattern of patients with winter seasonal affective disorder with and without light treatment was determined by positron emission tomography. Compared with controls, patients with seasonal affective disorder with and without light treatment had globally lower metabolic rates, relatively lower superior medial frontal cortex rates, and somewhat higher basal ganglia rates. Patients receiving light treatment had a relatively higher rate in an occipital region of interest containing the primary visual cortex. Patients without light treatment had relatively higher metabolic rates in right parietal and medial orbitofrontal cortex and lower rates in the left parietal cortex. Patients not receiving light treatment had a hemispheric metabolic asymmetry (left greater than right) for the midprefrontal cortex located 67 mm above the canthomeatal line. The right side of this region, previously found reduced in manic-depressive illness and schizophrenia, was decreased primarily in patients with seasonal affective disorder with fewer atypical depressive symptoms. These "abnormal" prefrontal and parietal cortex regions appeared highly "coupled" in the patients with seasonal affective disorder.

Adult↗

Frequency specific effects of stroboscopic rearing in the visual cortex of the rabbit.

Rearing animals in stroboscopic illumination deprives those animals of the experience of visual motion. In the rabbit, stroboscopic rearing produces a significant alteration in the response properties of cells in the visual cortex, demonstrating that the rabbit visual system is susceptible to environmental manipulation during early postnatal life. Response properties were determined for single units recorded in the primary visual cortex of 3 groups of rabbits. One group had been reared from birth to 2 months of age at a stroboscopic flash frequency of 8 Hz, a second group was raised at a flash frequency of 4 Hz and a third was reared normally. Compared to normal rabbits, rabbits reared at 8 Hz showed a reduction in the proportion of orientation selective cells which were also direction-selective, and there was an increase in the proportion of cells responsive to stroboscopic flashes. There was no reduction, however, in the overall proportion of orientation-selective cells. This contrasts with the finding for the rabbits raised at a flash frequency of 4 Hz. In addition, cortical cells in the rabbits raised at 8 Hz responded to frequencies of stroboscopic flashes which were significantly higher than the frequencies found for cells in the rabbits raised at 4 Hz. The effects of stroboscopic rearing on the rabbit visual cortex are dependent, therefore, on the flash frequency experienced by the rabbits during development.

Animals↗

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning.

Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

Action Potentials↗

Axonal processes and neural plasticity.I: Ocular dominance columns.

We present two related computational models of ocular dominance column formation. Both address nervous system plasticity in terms of sprouting and retraction of axonal processes rather than changes in synaptic strength implied by synapse-specific Hebbian models. We employ statistical mechanics to simulate changes in the pattern of network connectivity. Our formalism uses the concept of an energy function, which we interpret as related to the levels of target-generated neurotrophins for which afferents compete. In contrast, synapse-specific Hebbian models impose synaptic normalization, for which there is little experimental evidence, in order to induce competition. Our models make many predictions which require experimental investigation. We suggest that the absence of monocular deprivation effects in the optic tectum may be due to a tendency of amphibian retinal ganglion cells to preserve the complexity of their terminal arbors. One model raises the possibility that boundaries separating columns in the mammalian cortex are poorly innervated if they have been formed by complete but asynchronous retinal activation. Both models exhibit a phase transition, suggesting a discontinuity in the transition from a binocular cortex to one possessing ocular dominance columns. Finally, our other model could account for the perpendicularity of ocular dominance columns to the boundary of the primary visual cortex while admitting of less ordered central patterns.

Animals↗

Response linearity in primary auditory cortex of the ferret.

The responses of neurons within the primary auditory cortex (A1) of the ferret elicited by broadband dynamic spectral ripple stimuli were examined over a range of ripple spectral densities and ripple velocities. The large majority of neurons showed modulated responses to these stimuli and responded most strongly at low ripple densities and velocities. The period histograms of their responses were subjected to Fourier analysis, and the ratio of the magnitudes of the f1 and fo (DC) components of these responses were calculated to give a quantitative index of response linearity. For 82 out of 396 neurons tested (20.7%) this ratio remained above 1.0 over the entire range of ripple densities and velocities. These neurons were classified as 'consistently linear'. A further 134/396 (33.8%) of neurons maintained an f1/f0 ratio above 1.0 for either a range of ripple densities at a fixed ripple velocity, or over a range of ripple velocities at a specific ripple density, and were classified as 'locally linear'. Interestingly, for the superficial layers of the primary auditory cortex, consistently linear and locally linear neurons outnumbered nonlinear neurons by a 2:1 ratio. The converse was true for the deep layers. Unlike in primary visual cortex, where f1/f0 ratios have been reported to exhibit a bimodal distribution with a minimum at f1/f0 = 1, f1/f0 ratios for A1 are unimodally distributed with a peak at f1/f0 = 1.

Acoustic Stimulation↗

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.

Animals↗

Transient immunoglobulin-like molecules are present in the subplate zone and cerebral cortex during postnatal development.

A monoclonal antibody (mAb SP-1) labels subplate neurons of the cat visual cortex but does not stain the remnants of the subplate neuronal population that comprise the interstitial cells of adult cortical white matter. mAb SP-1 was shown previously to recognize a cytosolic polypeptide of 56 kDa (Naegele et al., 1991). We have now characterized the distribution of SP-1 immunoreactive neurons in the visual cortex and carried out additional biochemical studies at a range of postnatal ages in various tissues. Brain, liver and serum were found to contain the previously identified 56 kDa polypeptide. This polypeptide was also recognized by a cat immunoglobulin antiserum. The epitope recognized by mAb SP-1 was present on cat IgG Fc fragment but not cat IgG Fab fragment. By 4 weeks postnatal, levels of the 56 kDa antigen decreased in cortex and an additional higher molecular weight SP-1 reactive polypeptide of 75 kDa was detected. In the mature cortex, both polypeptides were absent from cytosolic fractions. Immunocytochemical staining comparing the distributions of SP-1 (SP-1+) and anti-IgG (Ig+) immunoreactive neurons showed complete colocalization in subplate neurons beneath primary visual cortex. By 4 weeks, some pyramidal neurons in cortical areas 17 and 18 were weakly positive for SP-1 but negative for IgG. At subsequent ages, the immunoreactive staining became progressively fainter until it was no longer detectable in white or gray matter of adult cat visual cortex.

Amino Acid Sequence↗

Properties of horizontal and vertical inputs to pyramidal cells in the superficial layers of the cat visual cortex.

The purpose of this study is to elucidate the integrative input mechanisms of pyramidal cells receiving horizontally projecting axon collaterals (horizontal projection) and vertical input from layer IV. We performed whole-cell recordings from pyramidal cells in layer II/III and focally activated other single pyramidal cells monosynaptically connected via long-distance horizontal (LH) projections (the distance between presynaptic and postsynaptic cells was 350-1200 micrometer) in slice preparations of the kitten primary visual cortex. In addition, presynaptic single fibers in layer IV (vertical input) and/or short-distance horizontal (SH) inputs from neighboring single pyramidal cells (distance within 100 micrometer) in layer II/III were activated. Unitary EPSPs evoked by the activation of LH and SH connections had smaller amplitude and larger coefficient of variation than those evoked by stimulating the vertical input. Paired-pulse stimulation of the LH and SH inputs caused the depression of the second EPSP, whereas that of vertical inputs caused either facilitation or depression of the second EPSP. The EPSPs evoked by simultaneous activation of LH and vertical inputs summated linearly at the resting membrane potential. However, the EPSPs evoked by stimulation of the two inputs were nonlinearly (supralinearly) summated when the postsynaptic membrane was depolarized to a certain level. Similar EPSP interaction was observed in response to simultaneous activation of the LH and SH inputs.

Animals↗

Temporal relationship between action and visual outcome modulates brain activation: an fMRI study.

Monitoring the visual outcome of our actions is critical to our visuo-motor behavior. To investigate the neural basis of monitoring visual change produced by self-movement, we examined the temporal relationship between manual depression of a button and visual feedback on activation of the brain. Six neurologically normal subjects participated in 3 experiments (synchronous, delayed, and visual [control]). Magnetic resonance (MR) images of their brains were acquired during the experiments using a scanner operating at 3T. In the synchronous experiment, subjects pressed a button at self-paced intervals and received synchronous visual stimuli in response. In the delayed experiment, visual stimuli were presented with a delay after subjects pressed a button at self-paced intervals. In the control experiment (visual experiment), subjects did not press the button, but viewed visual stimuli generated by a computer at random intervals. In the synchronous experiment, activation in the cerebellum and right parietal lobe was stronger than in the delayed experiment, whereas activation in the primary visual cortex was weaker than in the delayed and visual experiments. These results suggest that visual outcomes produced synchronously with action are processed in the cerebellum and the parietal area for the organization of optimal motor behavior, rather than in the primary visual area that is known to process the visual properties of external objects. The cerebellar signal related to visuo-motor contingency may modulate the cortical processing of visual input that is synchronous with action.

Adult↗

Antipsychotic treatment induces alterations in dendrite- and spine-associated proteins in dopamine-rich areas of the primate cerebral cortex.

BACKGROUND: Mounting evidence indicates that long-term treatment with antipsychotic medications can alter the morphology and connectivity of cellular processes in the cerebral cortex. The cytoskeleton plays an essential role in the maintenance of cellular morphology and is subject to regulation by intracellular pathways associated with neurotransmitter receptors targeted by antipsychotic drugs. METHODS: We have examined whether chronic treatment with the antipsychotic drug haloperidol interferes with phosphorylation state and tissue levels of a major dendritic cytoskeleton-stabilizing agent, microtubule-associated protein 2 (MAP2), as well as levels of the dendritic spine-associated protein spinophilin and the synaptic vesicle-associated protein synaptophysin in various regions of the cerebral cortex of rhesus monkeys. RESULTS: Among the cortical areas examined, the prefrontal, orbital, cingulate, motor, and entorhinal cortices displayed significant decreases in levels of spinophilin, and with the exception of the motor cortex, each of these regions also exhibited increases in the phosphorylation of MAP2. No changes were observed in either spinophilin levels or MAP2 phosphorylation in the primary visual cortex. Also, no statistically significant changes were found in tissue levels of MAP2 or synaptophysin in any of the cortical regions examined. CONCLUSIONS: Our findings demonstrate that long-term haloperidol exposure alters neuronal cytoskeleton- and spine-associated proteins, particularly in dopamine-rich regions of the primate cerebral cortex, many of which have been implicated in the psychopathology of schizophrenia. The ability of haloperidol to regulate cytoskeletal proteins should be considered in evaluating the mechanisms of both its palliative actions and its side effects.

Animals↗

Putting spatial attention on the map: timing and localization of stimulus selection processes in striate and extrastriate visual areas.

This study investigated the cortical mechanisms of visual-spatial attention in a task where subjects discriminated patterned targets in one visual field at a time. Functional magnetic imaging (fMRI) was used to localize attention-related changes in neural activity within specific retinotopic visual areas, while recordings of event-related brain potentials (ERPs) traced the time course of these changes. The earliest ERP components enhanced by attention occurred in the time range 70-130 ms post-stimulus onset, and their neural generators were estimated to lie in the dorsal and ventral extrastriate visual cortex. The anatomical areas activated by attention corresponded closely to those showing increased neural activity during passive visual stimulation. Enhanced neural activity was also observed in the primary visual cortex (area V1) with fMRI, but ERP recordings indicated that the initial sensory response at 50-90 ms that was localized to V1 was not modulated by attention. Modeling of ERP sources over an extended time range showed that attended stimuli elicited a long-latency (160-260 ms) negativity that was attributed to the dipolar source in area V1. This finding is in line with hypotheses that V1 activity may be modulated by delayed, reentrant feedback from higher visual areas.

Adolescent↗

Positron emission tomography with deoxyglucose-F18 imaging of sleep.

Positron emission tomography with deoxyglucose-F18 was obtained during nighttime sleep in 36 normal volunteers, 12 studied in rapid eye movement sleep (REM period 2), 12 in nonREM sleep, and 12 while awake with eyes closed. Metabolic rate was higher throughout the cortex in REM than nonREM sleep, with differences most marked in the cingulate and frontal cortex, thalamus, and visual association areas. Whole-brain metabolic rates in the waking condition were intermediate between those in REM and nonREM sleep. Metabolism in the primary visual cortex and parts of the lateral temporal lobe was relatively constant in the REM/nonREM conditions. REM sleep did not differ from either the nonREM or waking conditions in hemispheric lateralization of metabolic activity. Compared with REM sleep, nonREM sleep was associated with significantly lower metabolic rates in the temporal and occipital regions, as well as the thalamus.

Adult↗

Parallel-distributed processing in olfactory cortex: new insights from morphological and physiological analysis of neuronal circuitry.

A working hypothesis is proposed for piriform cortex (PC) and other olfactory cortical areas that redefines the traditional functional roles as follows: the olfactory bulb serves as the primary olfactory cortex by virtue of encoding 'molecular features' (structural components common to many odorant molecules) as a patchy mosaic reminiscent of the representation of simple features in primary visual cortex. The anterior olfactory cortex (that has been inappropriately termed the anterior olfactory nucleus) detects and stores correlations between olfactory features, creating representations (gestalts) for particular odorants and odorant mixtures. This function places anterior olfactory cortex at the level of secondary visual cortex. PC carries out functions that have traditionally defined association cortex--it detects and learns correlations between olfactory gestalts formed in anterior olfactory cortex and a large repertoire of behavioral, cognitive and contextual information to which it has access through reciprocal connections with prefrontal, entorhinal, perirhinal and amygdaloid areas. Using principles derived from artificial networks with biologically plausible parallel-distributed architectures and Hebbian synaptic plasticity (i.e. adjustments in synaptic strength based on locally convergent activity), functional proposals are made for PC and related cortical areas. Architectural features incorporated include extensive recurrent connectivity in anterior PC, predominantly feedforward connectivity in posterior PC and backprojections that connect distal to proximal structures in the cascade of olfactory cortical areas. Capabilities of the 'reciprocal feedforward correlation' architecture that characterizes PC and adjoining higher-order areas are discussed in some detail. The working hypothesis is preceded by a review of relevant anatomy and physiology, and a non-quantitative account of parallel-distributed principles. To increase the accessibility of findings for PC and to advertise its substantial potential as a model for experimental and modeling analysis of associative processes, parallels are described between PC and the hippocampal formation, inferotemporal visual cortex and prefrontal cortex.

Animals↗

Calbindin immunoreactivity alternates with cytochrome c-oxidase-rich zones in some layers of the primate visual cortex.

Calcium ions have a pivotal role in many neuronal activities, but little is known about their involvement in the cortical processing of visual information. Using immunohistochemical methods, we have now detected a calcium-binding protein, calbindin-D-28K, which may confer on certain compartments of cortical area 17 the ability to modulate Ca2+ metabolism. Thus, calbindin occurs in the primate striate cortex in a pattern almost complementary to that displaying strong cytochrome c-oxidase activity. From this and other observations, we deduce that the distribution of calbindin-immunoreactive sites corresponds mainly to extra-geniculocortical connections of the primary visual cortex. This implies that the geniculocortical and extra-geniculocortical compartments of area 17 differ in an intracellular system for Ca2+ homeostasis.

Animals↗

Bypassing V1: a direct geniculate input to area MT.

Thalamic nuclei are thought to funnel sensory information to the brain's primary cortical areas, which in turn transmit signals afresh to higher cortical areas. Here we describe a direct projection in the macaque monkey from the lateral geniculate nucleus (LGN) to the motion-selective middle temporal area (MTor V5), a cortical area not previously considered 'primary'. The constituent neurons are mostly koniocellular, send virtually no collateral axons to primary visual cortex (V1) and equal about 10% of the V1 population innervating MT. This pathway could explain the persistence of motion sensitivity in subjects following injury to V1, suggesting more generally that residual perception after damage in a primary area may arise from sparse thalamic input to 'secondary' cortical areas.

Animals↗