Marc F. Schmidt

Sustained increase in intracellular calcium promotes neuronal survival.

Ciliary ganglion neurons, half of which normally suffer developmental death in the embryo, will survive in culture in medium supplemented with depolarizing concentrations of potassium. It is not known how elevated potassium acts inside the cell to promote survival. We report here that depolarizing concentrations of extracellular potassium promote neuronal survival by causing a sustained increase in intracellular calcium. Raising extracellular potassium from 5 to 40 mM, an optimal concentration for survival, caused a sustained increase in intracellular calcium from 250 nM to greater than 600 nM. By 26 hr, at which time greater than 90% of neurons in 5 mM potassium had died, the calcium concentration of neurons in 40 mM potassium was still above 400 nM. Reduction of extracellular potassium from 40 to 5 nM, which prevents the increase in survival, also reduced intracellular calcium back to rest levels. PN200–110, a dihydropyridine calcium channel blocker that inhibits the survival-promoting effect of elevated potassium, also prevented and reversed the potassium,-mediated increase in intracellular calcium. In addition, there was a strong, quantitative correlation between the percentage of neuronal survival and the intracellular calcium concentration over a wide range of extracellular potassium concentrations. These results suggest that elevated potassium opens dihydropyridine-sensitive calcium channels, causing a sustained increase in intracellular calcium that quantitatively determines the number of surviving neurons.

Gating of auditory responses in the vocal control system of awake songbirds

Nucleus HVc of the avian song system is a forebrain structure critical in song production, perception and learning. Here we show that most HVc neurons that respond to auditory stimuli under anesthesia show no responses to the same stimulus in the awake, unrestrained bird. This suppression of auditory responses in awake birds does not occur in the forebrain field L complex, which is one of the auditory input stages for HVc. Gating of auditory input at the junction between the auditory and vocal control system may be essential for regulating auditory feedback signals necessary for song learning and maintenance.

LAMININ AND FIBRONECTIN GUIDEPOSTS SIGNAL SUSTAINED BUT OPPOSITE EFFECTS TO PASSING GROWTH CONES

Guidepost cells are known to alter the behavior of growth cones in vivo, yet the nature of communication and the type of signals employed are largely undefined. The present study demonstrates that model guideposts, composed of a single molecular species, are sufficient to change the navigation and the behavior of advancing growth cones well beyond the time of contact. Laminin on model guideposts caused a sustained increase in growth cone velocity, whereas fibronectin led to a sustained decrease. A spatially discrete array of multiple laminin-model guideposts maintained increased growth rates on fibronectin, as expected for homogeneous laminin, and also provided unambiguous directional guidance information. Laminin-evoked growth cone responses required activation of protein kinase C-dependent intracellular signalling mechanisms.

Brainstem and Forebrain Contributions to the Generation of Learned Motor Behaviors for Song

Brainstem nuclei have well established roles in generating nonlearned rhythmic behaviors or as output pathways for more complex, forebrain-generated behaviors. However, the role of the brainstem in providing information to the forebrain that is used to initiate or assist in the control of complex behaviors is poorly understood. In this study, we used electrical microstimulation in select nuclei of the avian song system combined with recordings of acoustic and respiratory output to examine how forebrain and brainstem nuclei interact in the generation of learned vocal motor sequences. We found that brief stimulation in the forebrain nuclei HVC (used as a proper name) and RA (robust nucleus of the arcopallium) caused a short-latency truncation of ongoing song syllables, which ultimately led to a cessation of the ongoing motor sequence. Stimulation within the brainstem inspiratory-related nucleus paraambigualis, which receives input from RA and projects back to HVC via the thalamus, caused syllable truncations and interruptions similar to those observed in HVC and RA. In contrast, stimulation in the tracheosyringal portion of the hypoglossal nucleus, which innervates the syrinx (the avian vocal organ) but possesses no known projections back into the song system, did not cause any significant changes in the song motor pattern. These findings suggest that perturbation of premotor activity in any nucleus within the recurrent song system motor network will disrupt the ongoing song motor sequence. Given the anatomical organization of this network, our results are consistent with a model in which the brainstem respiratory nuclei form an integral part of the song motor programming network by providing timing signals to song control nuclei in the forebrain.

Noradrenergic Inputs Mediate State Dependence of Auditory Responses in the Avian Song System

Norepinephrine (NE) plays a complex role in the behavioral state-dependent regulation of sensory processing. However, the role of forebrain NE action in modulating high-order sensory activity has not been directly addressed. In this study, we take advantage of the discrete, feedforward organization of the avian song system to identify a site and mechanism of NE action underlying state-dependent modulation of sensory processing. We have developed an experimental paradigm in which brief arousal repeatedly suppresses song system auditory responsiveness. Using pharmacological manipulations in vivo, we show that infusion of α-adrenergic antagonists into the NIf (nucleus interfacialis of the nidopallium), an auditory forebrain area, blocks this state-dependent modulation. We also demonstrate dose-dependent enhancement and suppression of song system auditory response properties by NE and adrenergic agonists. Our results demonstrate that noradrenergic release in a single forebrain area is a mechanism underlying behavioral state-dependent regulation of auditory processing in a neural system specialized for vocal learning.

Discovery of a New Gravitational Lens System

A new gravitational lens system, the triple radio source MG2016+112, has been discovered. Five emission lines at a redshift of 3.2733�0.0014 have been identified in the spectra of two stellar objects of magnitude 22.5 coincident with radio components 3.4 arc seconds apart. The lines are the narrowest ever observed in objects at such a large redshift. The redshift of a 23rd-magnitude extended optical object coincident with the third radio component has not been determined spectroscopically, but its known optical properties are consistent with those of a giant elliptical galaxy with a redshift of about 0.8.

Bottom-up activation of the vocal motor forebrain by the respiratory brainstem.

Brainstem motor structures send output commands to the periphery and are dynamically modulated by telencephalic inputs. Little is known, however, about ascending brainstem control of forebrain motor structures. Here, we provide the first evidence for bottom-up activation of forebrain motor centers by the respiratory brainstem. We show that, in the avian vocal control system, activation of the brainstem inspiratory nucleus paraambigualus (PAm), a likely homolog of the mammalian rostral ventral respiratory group, can drive neural activity bilaterally in the forebrain vocal control nuclei HVC (used as a proper name) and the robust nucleus of the arcopallium (RA). Furthermore, this activation is abolished by lesions of nucleus uvaeformis (Uva), a thalamic nucleus necessary for song production. We identify a type of bursting neuron within PAm whose activity is correlated, in an Uva dependent manner, to bursting activity in RA, rather than to the respiratory rhythm, and is robustly active during the production of stimulus evoked vocalizations. Because this ascending input results in cross-hemisphere activation, our results suggest a crucial role for the respiratory brainstem in coordinating forebrain motor centers during vocal production.

High-resolution CCD imaging and derived gravitational lens models of 2237+0305

Images of the gravitational lens 2237+0305 acquired in good seeing have resolved the system into at least five components within the central few arsec of the object: the galaxy nucleus and four point sources in a ringlike formation approximately centered on the galaxy. It is found that the four point sources are distinctly bluer than the galaxy, but that they do not have identical colors. The observed configuration is well reproduced by a simple model that assumes that the four objects are images of the quasar and that the lens is a constant mass-to-light ratio, elliptical, de Vaucouleurs bulge. 29 references.

Bilateral Control and Interhemispheric Coordination in the Avian Song Motor System

Abstract: Birdsong is a complex learned motor behavior controlled by an interconnected network of vocal control nuclei that are present in both cerebral hemispheres. Unilateral lesions of song nuclei in the left or the right hemisphere result in different effects on song structure, suggesting that normal song output results from the activation of two parallel but functionally different motor pathways. Because each syringeal half is innervated primarily by ipsilateral motor structures and activity in both halves is tightly coordinated during singing, motor commands originating from both hemispheres must be tightly coordinated to produce the appropriate vocal output. This coordination occurs despite the absence of direct interhemispheric connections between song control nuclei. In this article, we discuss how motor commands in nucleus HVC, a key forebrain song control region, are coordinated by precisely timed inputs that act to synchronize premotor activity in both hemispheres. Synchronizing inputs are tightly linked to syllable and note onset, which suggests that bilaterally organized circuits in the midbrain or brainstem act in specifying higher‐order song features, such as duration, order, and possibly even structure of individual song syllables. The challenge ahead lies in identifying the networks that generate the synchronizing timing inputs and to determine how these inputs specify the motor commands in HVC. Resolving these issues will help us gain a better understanding of how pattern‐generating networks in the midbrain/brainstem interface with forebrain circuits to produce complex learned behaviors.

What birdsong can teach us about the central noradrenergic system

Increasing evidence indicates that the noradrenergic system plays a key role in biasing the nervous system towards producing behaviors that help animals adapt to constantly changing environments. Most of the studies investigating noradrenergic function are performed in animals that have a limited repertoire of tractable natural behaviors. Songbirds, in contrast, with their rich set of precisely quantifiable vocal behaviors, provide a unique model system to study the noradrenergic system. An additional advantage of this system is the existence of a well-defined neural circuit, known as the song system, that is necessary for the production, learning and perception of song and can be studied at many different levels. These include the ability to investigate the effect of norepinephrine on synaptic function using brain slices, identifying its influence on singing-related gene expression and monitoring its impact on the activity of single neurons recorded in awake behaving birds. In this review article, we describe the similarities and differences, both anatomical and functional, between the avian and mammalian noradrenergic system and its role in sensory processing, learning, attention and synaptic modulation. We also describe how the noradrenergic system influences motor production, an under-explored aspect of norepinephrine function in mammalian studies. We argue that the richness of behaviors observed in songbirds provides a unique opportunity to study the noradrenergic system in a highly integrative manner that will ultimately provide important insights into the role of this system in normal behavior and disease.