Christian M. Müller

Tissue plasminogen activator mediates reverse occlusion plasticity in visual cortex

Preventing visual input to one eye (monocular deprivation) in early postnatal development reduces cortical responses to stimulation of the deprived eye, with a significant loss of thalamocortical connections. These effects are reversible by opening the deprived eye and closing the previously open eye (reverse occlusion). We show that intracortical blockade of tissue plasminogen activator or plasmin selectively prevents recovery of cortical function and thalamic neuron size during reverse occlusion, without affecting the monocular deprivation response. Therefore, a proteolytic cascade consisting of plasmin generated by tissue plasminogen activator may selectively mediate reverse-occlusion-induced cortical plasticity, perhaps via structural remodeling of axons.

Possible role of S-100 in glia—Neuronal signalling involved in activity-dependent plasticity in the developing mammalian cortex

Using Western blot analyses and a quantitative ELISA, we identified the presence and developmental accumulation of the astroglial S-100 protein(s) in rat and cat visual cortex. There is a steep rise in the S-100 content, comprising mainly S-100 beta, during the time period of highest cortical malleability in both species. A possible role of the astroglial S-100 protein(s) in experience-dependent plasticity of the visual cortex of kittens was tested by infusing antiserum against this protein during the critical period for cortical malleability. Following 1 week of monocular deprivation, the ocular dominance of single cells in the visual cortex was investigated. The vast majority of cells in the hemispheres infused with anti-S-100 serum maintained binocular responses. This finding suggests that extracellular S-100 protein is essential for ocular-dominance plasticity. Infusion of S-100 beta during the critical period of cortical malleability had no effect on deprivation-induced ocular-dominance plasticity, but interfered with the experience-dependent refinement of orientation selectivity of visual cortical neurons. It is suggested that S-100 beta may play an important role in the refinement of cortical circuitries by selectively affecting active or activated neuronal compartments. As S-100 beta is synthesized in astroglial cells, the effects on neuronal plasticity imply that glia-neuronal information transfer occurs during activity-dependent plasticity. Possible underlying mechanisms are discussed on the basis of current knowledge on the S-100 protein family, especially S-100 beta (Marshak, 1990).

γ-Aminobutyric acid immunoreactivity in brainstem auditory nuclei of the chicken

Using an antiserum directed against gamma-aminobutyric acid (GABA), the presence of presumed GABAergic neurons is demonstrated in the chicken auditory brainstem nuclei: nucleus laminaris, nucleus angularis, superior olive, and the ventral nuclei of the lateral lemniscus. Nucleus magnocellularis contains no immunopositive neurons but numerous GABA-positive terminals surrounding the cells. Terminal labeling is also present in the other auditory nuclei, though scarcer and not always associated with cell bodies. These data suggest an involvement of GABAergic inhibition in auditory processing in the lower auditory pathway of birds.

Looking for the roots of cortical sensory computation in three-layered cortices

Despite considerable effort over a century and the benefit of remarkable technical advances in the past few decades, we are still far from understanding mammalian cerebral neocortex. With its six layers, modular architecture, canonical circuits, innumerable cell types, and computational complexity, isocortex remains a challenging mystery. In this review, we argue that identifying the structural and functional similarities between mammalian piriform cortex and reptilian dorsal cortex could help reveal common organizational and computational principles and by extension, some of the most primordial computations carried out in cortical networks.

Development of layers, maps and modules

Developing neuronal cell sheets acquire position-specific features by mechanisms that differ in radial and tangential dimensions. These features include guiding cues for axonal growth and targeting that are used, for example, in map formation. Recent evidence supports the notion that graded distributions of molecules are involved in growth cone navigation and axonal branching. In addition, activity-dependent processes are important determinants of functional architecture, especially with respect to modular organization.

Seasonal changes in astrocytes parallel neuronal plasticity in the song control area HVc of the canary.

In the song control area HVc of the canary, intercellular dye‐coupling among astrocytes was studied by intracellular injection of neurobiotin into identified single astrocytes. Injection of individual astrocytes into acute slices resulted in dye spread to neighboring astrocytes, covering a sphere of up to 1 mm in diameter. The astrocytic nature of the dye‐coupled cells was verified by double labeling of neurobiotin‐filled cells with antisera for the astrocytic filament proteins GFAP or vimentin. The similarity in the number of dye‐coupled cells and the total number of astrocytes labeled by immunocytochemical markers indicate that dye‐coupling is specific for astrocytes and labels almost the entire local astrocytic population. Within the major nucleus for vocal control (HVc), approximately 25% more astroglial cells were present than in the surrounding forebrain tissue. There is no apparent hindrance of dye spread at the border of the HVc. The density of dye‐coupled astrocytes and the expression of cytoskeletal filament proteins differed markedly between the reproductive period in spring and the quiescent period in autumn. While vimentin is the major astroglial filament in autumn, GFAP is strongly expressed in spring. The density of dye‐coupled astrocytes reveals a marked increase in the reproductive period, followed by a reduction in autumn. The data indicate that the astrocytic population in the avian forebrain undergoes significant changes coincident with the known functional changes in the vocal control nuclei during periods of song production. GLIA 27:88–100, 1999.

CRITICAL PERIOD-DEPENDENT REDUCTION OF THE PERMISSIVENESS OF CAT VISUAL CORTEX TISSUE FOR NEURONAL ADHESION AND NEURITE GROWTH

During postnatal development, the visual cortex undergoes an experience‐dependent refinement of its circuitry. This process includes synapse formation, as well as synapse elimination. Both mechanisms appear to be restricted to a limited ‘critical period’ which lasts for ∼2 months in cats. We tested whether the termination of the critical period for cortical malleability is paralleled by changes in the growth permissiveness of the tissue. These changes may inhibit progressive reorganization of functional circuitries mediated by axon growth. Embryonic cortical neurons were cultured on unfixed cryostat sections of the visual cortex obtained from cats aged 2–50 weeks. After 2–3 days in vitro the distribution of viable cells and the percentage of neurite‐bearing cells were determined and analysed with respect to the developmental age and subdivisions of the underlying tissue substrate. It was shown that cell adhesion and neurite formation are correlated with the developmental age of the substrate tissue and the time period of myelination. While embryonic neurons adhered and survived on grey and white matter tissue from 2‐ and 4‐week‐old kittens, there was a significant reduction in cell adhesion on the myelinated white matter regions of the tissue sections of older animals. Quantitative analyses showed that neurite formation by cultured neurons also became successively impaired on grey and white matter areas of tissue substrates, corresponding to the time course of the critical period for cortical malleability. On grey matter tissue this effect was most pronounced between the second and sixth postnatal weeks. The effects were not antagonized by coating the substrate sections with the growth‐promoting molecule laminin. It is therefore proposed that neurite growth‐inhibiting factors, most probably associated with central nervous system myelin, are gradually expressed postnatally and may contribute to the termination of the critical period in the visual cortex of cats.

Differential effects of acetylcholine in the chicken auditory neostriatum and hyperstriatum ventrale ― studies in vivo and in vitro

Summary1.The effect of acetylcholine (ACh) on the response properties of single units in the caudal auditory telencephalon was studied both in awake chickens and in an in vitro slice preparation.2.Two types of electrophysiological behavior in response to ACh were observed: an inhibition of cell firing typical for the majority of neurons in the auditory hyperstriatum ventrale and a facilitation of neuronal responses seen predominantly in neostriatal auditory units.3.The facilitatory effect of ACh is also present in hyperstriatal cells, but is usually dominated by an indirect inhibition.4.ACh-induced facilitation on single unit responses could be mimicked in awake birds by applying potentially arousing sensory stimuli.5.The effects of ACh are antagonized by the muscarinic receptor blocker scopolamine.6.Inhibitory responses can also be antagonized by the GABA-antagonist bicuculline and thus can be attributed to an ACh-induced activation of GABAergic inhibitory interneurons. Evidence is given that the facilitatory responses result from a closure of voltage-dependent potassium channels.7.The results are discussed with respect to a possible role of cholinergic afferents in telencephalic processing of auditory information and in comparison with the cholinergic influences in the mammalian neocortex.

Spatial Information in a Non-retinotopic Visual Cortex

Turtle dorsal cortex (dCx), a three-layered cortical area of the reptilian telencephalon, receives inputs from the retina via the thalamic lateral geniculate nucleus and constitutes the first cortical stage of visual processing. The receptive fields of dCx neurons usually occupy the entire contralateral visual field. Electrophysiological recordings in awake and anesthetized animals reveal that dCx is sensitive to the spatial structure of natural images, that dCx receptive fields are not entirely uniform across space, and that adaptation to repeated stimulation is position specific. Hence, spatial information can be found both at the single-neuron and population scales. Anatomical data are consistent with the absence of a clear retinotopic mapping of thalamocortical projections. The mapping and representation of visual space in this three-layered cortex thus differ from those found in mammalian primary visual cortex. Our results support the notion that dCx performs a global, rather than local, analysis of the visual scene.

Cholinergic mechanisms in the telencephalon of cat and chicken.

Cholinergic afferents to the mammalian cortex have gained considerable interest because of their possible involvement in learning and memory (Everitt et al., 1987; Rigdon and Pirch, 1986), as well as their role in attentional processing (Phillis, 1968; Singer, 1979). These afferents originate predominantly from several nuclei in the basal forebrain (Mesulam et al., 1983). Similar cholinergic afferents are known from non-mammalian species, e.g. from reptiles and birds (Mufson et al., 1984; Davies and Horn, 1983). Receptor binding studies also reveal the presence of acetylcholine receptors in the bird telencephalon (Wachtler, 1985). Like in mammalian species, sensory processing is impaired in birds when cholinergic antagonists are given (Cleeves and Green, 1982). These data indicate an overall similarity of the organization and effects of the cholinergic system in mammals and non-mammalian vertebrates.