Pattern motion representation in primary visual cortex is mediated by transcortical feedback.

A highly important question in visual neuroscience is to identify where in the visual system information from different processing channels is integrated to form the complex scenery we perceive. A common view to this question is that information is processed hierarchically because small and selective receptive fields in lower visual areas melt into larger receptive fields in specialized higher visual areas. However, a higher order area in which all incoming signals ultimately converge has not yet been identified. Rather, modulation of subthreshold influences from outside the classical receptive field related to contextual integration occurs already in early visual areas. So far it is unclear how these influences are mediated (Gilbert, 1998; Angelucci and Bullier, 2003; Gilbert and Sigman, 2007). In the present study, we show that feedback connections from a higher motion processing area critically influence the integration of subthreshold global motion cues in early visual areas. Global motion cues are theoretically not discernible for a local motion detector in V1, however, imprints of pattern motion have been observed in this area (Guo et al., 2004; Schmidt et al., 2006). By combining reversible thermal deactivation and optical imaging of intrinsic signals we demonstrate that feedback signals from the posteromedial suprasylvian sulcus are critical for the discrimination between global and local motions already in early visual areas. These results suggest that global features of the visual scenery are fed back to lower visual processing units in order to facilitate the integration of local cues into a global construct.

Interhemispheric asymmetries of the modular structure in human temporal cortex.

Language-relevant processing of auditory signals is lateralized and involves the posterior part of Brodmann area 22. We found that the functional lateralization in this area was accompanied by interhemispheric differences in the organization of the intrinsic microcircuitry. Neuronal tract tracing revealed a modular network of long-range intrinsic connections linking regularly spaced clusters of neurons. Although the cluster diameter was similar in both hemispheres, their spacing was about 20 percent larger in the left hemisphere. Assuming similar relations between functional and anatomical architecture as in visual cortex, the present data suggest that more functionally distinct columnar systems are included per surface unit in the left than in the right area 22.

Lucifer yellow filling of immunohistochemically pre-labeled neurons: a new method to characterize neuronal subpopulations.

We describe a new technique for the morphological characterization of immunohistochemically labeled neuron populations. We demonstrate that it is possible to fill neurons iontophoretically with Lucifer Yellow (LY) in fixed slices of cat visual cortex after the respective cells have been identified by indirect immunofluorescence for the neural cell adhesion molecule N-CAM 180, with the VC1.1 antibody or with an antibody against glutamate dehydrogenase (GAD). Morphological analysis of the injected cells at the light and electron microscopic level revealed that the N-CAM 180-positive neurons share the features of neuropeptidergic cortical interneurons. Depending on the antibody applied, the immunohistochemical treatment had little or no noticeable effect on the quality of LY filling or on the preservation of morphological details of the pre-labeled cells. This makes the method described ideally suited for the light and electron microscopic examination of selected, immunologically characterized neuron subpopulations.

The role of neurotrophins in developmental cortical plasticity.

PURPOSE: It has been proposed that experience dependent maturation and reorganization in the neocortex might be based on the activity dependent competition between different sets of axons for growth related molecules such as neurotrophins. In the present study we tested this hypothesis by examination of the effects of external administration of NGF and BDNF on the experience dependent rearrangement of thalamocortical connections after monocular deprivation (MD) in the developing cat visual cortex. METHODS: The visual cortices of kittens were infused intracortically either with BDNF, NGF or cytochrome C while the animals were subjected to MD for one week during the peak of the critical period (postnatal day 26 to postnatal day 40). Subsequently cortical neuronal responses were assessed with optical (optical imaging of intrinsic signals) and single unit recording techniques. RESULTS: In control hemispheres treated with cytochrome C, MD had caused the expected shift of OD towards the normal eye. Also hemispheres treated with NGF exhibited a strong shift of OD towards the open eye. However, in the BDNF infused hemispheres OD had shifted towards the deprived eye in a zone extending 2.5-3.5 mm from the infusion cannula and neurons had lost their orientation selectivity. In an adjacent transition zone both eyes activated the cortex equally well and responses were again tuned for orientation and at still larger distances OD was shifted towards the normal eye. CONCLUSIONS: The present data support the concept of an involvement of neurotrophins in cortical plasticity. However, our observations suggest for both neurotrophins, NGF and BDNF, a more complex role in the developing neocortex than serving simply as the substrate of an activity dependent competition process within the visual cortex. Moreover, the outcome of our study indicaties strong differences between BDNF and NGF concerning their involvement and locus of action in developmental plasticity.

Colocalization of different types of amyloid in the walls of cerebral blood vessels of patients suffering from cerebral amyloid angiopathy and spontaneous intracranial hemorrhage: a report of 5 cases.

Four cases of spontaneous intracranial hemorrhage (ICH) are described in which the diagnosis of a cerebral amyloid angiopathy (CAA) was made in the biopsy specimens. In one further case CAA was detected on autopsy after intracranial hemorrhage (ICH). Amyloidotic degeneration of the vessel walls appeared to be the most likely reason for the ICH which in these cases especially involved superficial neocortical regions. In all cases, co-deposition of A4beta-amyloid and ALlambda-amyloid was found in diseased leptomeningeal and cortical vessels. Besides CAA, all 5 patients suffered from other diseases which had affected the blood vessel walls such as atherosclerosis, diabetes mellitus or arterial hypertension. However, no signs of systemic amyloidosis could be detected in these cases. It is suggested that the observed co-deposition of 2 amyloid subtypes is based on the combination of 2 different diseases, one of which results in a local production of A4beta-amyloid in the tunica media of cerebral blood vessels and another one, e.g. arterial hypertension, which impairs the permeability of the blood vessels by affection of the tunica intima allowing for the pathological penetration of circulating immunoglobulin lambda-light chains into the vessel wall. Subsequently, the preexisting A4beta-amyloid might have induced the polymerization of the lambda-light chains to ALlambda-amyloid in the media of the vessels and could have aggravated the amyloidotic degeneration of the vessel walls.

The origin and topography of long-range intrinsic projections in cat visual cortex: a developmental study.

We investigated the morphological features of long range intrinsically projecting neurons and their pattern of axonal arborization in cat area 17 at different stages of postnatal development. In one set of experiments intracortically projecting cells were retrogradely labeled in vivo with rhodamine latex beads and then visualized by in vitro filling with Lucifer yellow. In another approach, intracortical fibers including the cells of origin were labeled postmortem in fixed brains with the lipophilic carbocyanine dye Dil. The results of this study indicate that the long-range intrinsic circuitry of the primary visual cortex develops in three major steps. The first step consists of the development of unclustered long-range axons in the two outer compartments of the cerebral cortex, layer I and the subplate. These early connections could serve as a scaffold for the organization of the tangential architecture of the neocortex as they originate from cells that are the first to receive synaptic input from extrinsic afferents. The second step consists of the outgrowth of horizontal axon collaterals originating from cells located in layers II-VI. During the first 2-3 weeks these connections still differ from those in the adult because they span shorter distances, originate more often from neurons with morphological features of nonpyramidal cells, and lack the precise clustering of the mature connections. The third step consists of a selection process that leads to the elimination of axon terminals from locations between the clusters of tangentially projecting neurons. This selection starts at the end of the second postnatal week and, hence, overlaps in time with the still proceeding elongation of axons and continues beyond the end of the fourth postnatal week when axon length has reached its maximal extent. This refinement process enhances the specificity of long-range connections and is probably influenced by visual experience.

Matching the modules: cortical maps and long-range intrinsic connections in visual cortex during development.

Visual cortical neurons exhibit a high degree of response selectivity and are grouped into small columns according to their response preferences. The columns are located at regularly spaced intervals covering the whole cortical representation of the visual field with a modular system of feature-selective neurons. The selectivity of these cells and their modular arrangement is thought to emerge from interactions in the network of specific intracortical and thalamocortical connections. Understanding the ontogenesis of this complex structure and contributions of intrinsic and extrinsic, experience-dependent mechanisms during cortical development can provide new insights into the way the visual cortex processes information about the environment. Available data about the development of connections and response properties in the visual cortex suggest that maturation proceeds in two distinct steps. In the first phase, mechanisms inherent to the cortex establish a crude framework of interconnected neural modules which exhibit the basic but still immature traits of the adult state. Relevant mechanisms in this phase are assumed to consist of molecular cues and patterns of spontaneous neural activity in cortical and corticothalamic interconnections. In a second phase, the primordial layout becomes refined under the control of visual experience establishing a fine-tuned network of connections and mature response properties.

Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex.

In the present study we examine the influence of neurotrophins on experience-dependent synaptic rearrangement in developing and adult visual cortex. Brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) was continuously infused into cortical area 18, and the functional architecture of the cortex was examined by use of optical and electrophysiological recording techniques. In kittens, BDNF infusion during monocular deprivation (MD) reversed the normally occurring ocular dominance (OD) shift towards the non-deprived eye so that the deprived eye dominated the BDNF-treated cortex after MD. Under conditions of equal activation of thalamocortical synapses, i.e. when animals were either subject to binocular deprivation (BD) or reared without deprivation, BDNF infusion did not disrupt binocularity of cortical units, but reversed the natural OD bias towards the contralateral eye in favour of the ipsilateral eye. In addition, BDNF treatment in kittens led to a loss of the orientation selectivity of cortical units irrespective of rearing conditions. In adult animals, BDNF influenced neither OD distributions nor orientation selectivity. The effect of NGF was markedly different. It was ineffective in kittens but in adult animals it caused a shift of OD towards the deprived eye when MD was combined with NGF infusion. However, in this case orientation selectivity was preserved. Thus, both neurotrophins have profound activity- and age-dependent effects on the functional architecture of the visual cortex. Moreover, our results indicate that simple substitution of neurotrophins in excess is unlikely to compensate for deprivation effects by preserving or restoring the normal functional architecture of the cortex.

Brain-derived neurotrophic factor reversed experience-dependent synaptic modifications in kitten visual cortex.

During a critical period of early postnatal development the functional architecture of the visual cortex is shaped by experience-dependent circuit selection following a Hebbian mechanism. One consequence is that monocular deprivation (MD) leads to competitive repression of the input from the deprived eye. Recently it has been proposed that this process might involve activity-dependent competition for neurotrophic substances because the synthesis of brain-derived neurotrophic factor (BDNF) is regulated by visual input. Here we investigate the effects of intracortical infusion of BDNF and nerve growth factor (NGF) on MD effects in the visual cortex. Neuronal responses were monitored with optical and single unit recording techniques in the visual cortex of kittens that had been infused intracortically either with BDNF, NGF or cytochrome C while subjected to MD for 1 week during the peak of the critical period. NGF or cytochrome C had no effect on the consequences of MD. After BDNF treatment, by contrast, ocular dominance (OD) shifted towards the deprived eye in a zone extending 2.5-3.5 mm from the infusion cannula, and neurons lost their orientation selectivity. At intermediate distances both eyes activated the cortex equally well and responses were again tuned for orientation; at still larger distances OD was shifted towards the normal eye. Thus, BDNF antagonizes the functional effects of MD and at high concentrations causes paradoxical disconnection of non-deprived afferents and a loss of orientation selectivity.