Faculty Bibliography

Song development provides an opportunity to study the mechanisms of vocal learning dynamically at molecular, cellular and systems levels, and across time scales ranging from minutes to months. To exploit these opportunities one needs to identify appropriate units, types and time scales of vocal change in nearly real time. The previous chapter by Tchernikovski et al. in this volume described techniques that make this research strategy feasible by allowing us to observe the song learning process through a 'temporal microscope' with variable degrees of resolution. In this chapter we summarize some of the new observations and raise hypotheses about the learning strategy of the bird. We focus on inferences that can be drawn from behavioral observations to the nature and complexity of the instructive signal that guides the vocal change (error-signal). We examine two effects: i) the emergence of syllable types and ii) changes in features within a syllable type. We found that different features of the same syllable change during different and sometimes disjointed developmental windows. We discuss the possibility that song imitation is achieved by correcting partial errors, and that features of those partial errors change adaptively during development, perhaps concurrently with changes in perception and in motor proficiency. Those hypotheses can be best examined by across levels investigation, starting from identifying critical moments in song development and recording of articulatory dynamics and neural patterns when only a few features of specific syllables undergo rapid changes. Such investigation could relate behavioral events to brain mechanisms that guide song learning from moment-to-moment and across extended periods

Current technology makes it possible to measure song development continuously throughout a vocal ontogeny. Here we briefly review some of the problems involved and describe experimental and analytic methods for automatic tracing of vocal changes. These techniques make it possible to characterize the specific methods the bird uses to imitate sounds: an automated song recognition procedure allows continuous song recording, followed by automated sound analysis that partition the song to syllables, extract acoustic features of each syllable, and summarize the entire song development process over time into a single database. The entire song development is then presentable in the form of images or movie clips. These Dynamic Vocal Development (DVD) maps show how each syllable type emerges, and how the bird manipulates syllable features to eventually approximate the model song. Most of the experimental and analytic methods described here have been organized into a software package, which also allows combined neural and sound recording to monitor changes in brain activity as vocal learning occurs. The software is available at http://ofer.sci.ccny.cuny.edu

Reward-seeking behaviors depend critically on dopamine signaling--dopamine neurons encode reward-related information by switching from tonic to phasic (burst-like) activity. Using guinea pig brain slices, we show that nicotine, like cocaine and amphetamine, acts directly in striatum where it enhances dopamine release during phasic but not tonic activity. This amplification provides a mechanism for nicotine facilitation of reward-related dopamine signals, including responses to other primary reinforcers that govern nicotine dependence in smokers

Like any other surgery requiring anesthesia, cochlear implantation in the first few years of life carries potential risks, which makes it important to assess the potential benefits. This study introduces a new method to assess the effect of age at implantation on cochlear implant outcomes: developmental trajectory analysis (DTA). DTA compares curves representing change in an outcome measure over time (i.e. developmental trajectories) for two groups of children that differ along a potentially important independent variable (e.g. age at intervention). This method was used to compare language development and speech perception outcomes in children who received cochlear implants in the second, third or fourth year of life. Within this range of age at implantation, it was found that implantation before the age of 2 resulted in speech perception and language advantages that were significant both from a statistical and a practical point of view. Additionally, the present results are consistent with the existence of a 'sensitive period' for language development, a gradual decline in language acquisition skills as a function of age

Intranasal (i.n.) administration of IFN beta-1b was examined as a route for targeted delivery to the rat central nervous system (CNS). Intranasal administration resulted in significant delivery throughout the CNS and cervical lymph nodes with low delivery to peripheral organs. At similar blood levels, intravenous (i.v.) administration of IFN beta-1b yielded 88-98% lower CNS levels and 100-1650% greater peripheral organ levels compared to intranasal. Autoradiography confirmed much greater delivery to the CNS with intranasal administration. Intranasally administered IFN beta-1b reached the brain intact and produced tyrosine phosphorylation of IFN receptor in the CNS. Intranasal administration offers a non-invasive method of drug delivery for multiple sclerosis (MS) that bypasses the blood-brain barrier (BBB) and directly targets the CNS and lymph nodes

In a companion paper, we reported that the goldfish oculomotor neural integrator could be trained to instability or leak by rotating the visual surround with a velocity proportional to +/- horizontal eye position, respectively. Here we analyze changes in the firing rate behavior of neurons in area I in the caudal brainstem, a central component of the oculomotor neural integrator. Persistent firing could be detuned to instability and leak, respectively, along with fixation behavior. Prolonged training could reduce the time constant of persistent firing of some cells by more than an order of magnitude, to <1 s. Normal visual feedback gradually retuned persistent firing of integrator neurons toward stability, along with fixation behavior. In animals with unstable fixations, approximately half of the eye position-related cells had upward or unstable firing rate drift. In animals with leaky fixations, two-thirds of the eye position-related cells showed leaky firing drift. The remaining eye position-related cells, generally those with lower eye position thresholds, showed a more complex pattern of history-dependent/predictive firing rate drift in relation to eye drift. These complex drift cells often showed a drop in maximum persistent firing rate after training to leak. Despite this diversity, firing drift and the degree of instability or leak in firing rates were broadly correlated with fixation performance. The presence, strength, and reversibility of this plasticity demonstrate that, in this system, visual feedback plays a vital role in gradually tuning the time course of persistent neural firing.

Persistent neural firing is of fundamental importance to working memory and other brain functions because it allows information to be held "online" following an input and to be integrated over time. Many models of persistent activity rely on some kind of positive feedback internal to the neural circuit concerned; however, too much feedback causes runaway firing (instability), and too little results in loss of persistence (leak). This parameter sensitivity leads to the hypothesis that the brain uses an error signal (external feedback) to tune the stability of persistent firing by adjusting the amount of internal feedback. We test this hypothesis by manipulating external visual feedback, a putative sensory error signal, in a model system for persistent firing, the goldfish oculomotor neural integrator. Over tens of minutes to hours, electronically controlled visual feedback consistent with a leaky or unstable integrator can drive the integrator progressively more unstable or leaky, respectively. Eye fixation time constants can be reduced >100-fold to <1 s. Normal visual feedback gradually retunes the integrator back to stability. Changes in the phase of the sinusoidal vestibulo-ocular response are consistent with integrator detuning, as are changes in ocular drift following eye position shifts compensating for brief passive head movements during fixations. Corresponding changes in persistent firing of integrator neurons are presented in the accompanying article. The presence, strength, and reversibility of the plasticity demonstrate that, in this system, external visual feedback plays a vital role in gradually tuning the stability of the neural integrator.

A coarse-grained representation of neuronal network dynamics is developed in terms of kinetic equations, which are derived by a moment closure, directly from the original large-scale integrate-and-fire (I&F) network. This powerful kinetic theory captures the full dynamic range of neuronal networks, from the mean-driven limit (a limit such as the number of neurons N --> infinity, in which the fluctuations vanish) to the fluctuation-dominated limit (such as in small N networks). Comparison with full numerical simulations of the original I&F network establishes that the reduced dynamics is very accurate and numerically efficient over all dynamic ranges. Both analytical insights and scale-up of numerical representation can be achieved by this kinetic approach. Here, the theory is illustrated by a study of the dynamical properties of networks of various architectures, including excitatory and inhibitory neurons of both simple and complex type, which exhibit rich dynamic phenomena, such as, transitions to bistability and hysteresis, even in the presence of large fluctuations. The implication for possible connections between the structure of the bifurcations and the behavior of complex cells is discussed. Finally, I&F networks and kinetic theory are used to discuss orientation selectivity of complex cells for 'ring-model' architectures that characterize changes in the response of neurons located from near 'orientation pinwheel centers' to far from them

Recent investigations have shown that a range of small molecules that reflect the metabolic state of a cell regulate the activity of potassium channels. For instance, hydrogen peroxide has been shown to activate adenosine 5'-triphosphate-sensitive potassium channels (K(ATP) channels), whereas heme closes certain calcium-activated potassium channels. Although the exact function of the beta subunit associated with voltage-gated potassium channels is still unclear, its crystal structure suggests that membrane excitability is directly coupled to metabolism.