Philip HS Jen - US grants

Many studies have demonstrated that the cerebellum receives auditory inputs. Cerebellar neurons responding to sound stimuli have been reported in cats, rats, monkeys and bats. With the exception of bats, cerebellar auditory neurons have only been isolated from the cerebellar vermis. In bats, auditory representation in the vermis and hemispheres has been studied. Species-specific differences in basic response properties have been described. It has been suggested that in sound localization, the cerebellum plays an important role in orienting an animal toward a sound source. However, directional response characteristics of cerebellar neurons to sound stimulation have not been well studied. How the cerebellar neurons code a moving sound and how the auditory space may be represented in the cerebellum have not been studied. The question of how cerebellar neurons may be related with sound emission has not been investigated either. The specific aims of this research proposal are to conduct electrophysiological studies to answer the following two major questions. 1) How do cerebellar neurons code directional information of a sound source? 2) What are the cerebellar activity during sound emission? The data obtained from this proposed research will contribute to our understanding of cerebellar function in bat echolocation behavior in particular, and to provide new insight on cerebellar function in general. Specifically, they may reveal the mechanism of coding of a sound stimulus by the cerebellar neurons and how the auditory space is registered in the cerebellum. The study of cerebellar activity during sound emission may reveal clues as how the cerebellum may regulate the activity of the motor pathways for vocalization. As the cytoarchitecture of the cerebellum of a bat, which will be used in this proposed research, is basically the same as that of a human, such data will undoubtedly contribute to the advancement of basic knowledge of our own cerebellum physiology.

This proposed research is a continual investigation of auditory signal processing in the mammalian brain. Using bats as a model, an electrophysiological study supplemented with histological confirmation will be conducted to examine the neural mechanism underlying the integration of acoustic spatial information in the pontine nuclei. In auditory signal transmission, the auditory information from the auditory cortex and the inferior colliculus terminate at the pontine nuclei which in turn project their axons as mossy fibers upon the cerebellum. Thus, the pontine nuclei are in a position to integrate messages originating at the auditory system before relaying to the cerebellum, which is believed to be involved in acoustically evoked motor orientation. Preliminary studies in my laboratory have demonstrated that pontine neurons responding to acoustic stimulus are broadly tuned to a wide band of stimulus frequency and often have multipeaked frequency threshold curves. Furthermore, these neurons are not tonotopically organized. These findings strongly suggest that pontine nuclei may encode some stimulus features beyond tonotopy. This proposal hypothesizes that the bat pontine nuclei plan an important role in integrating the processed echo information during the final phase of echolocation. Thus most pontine neurons should b maximally sensitive to a frontal sound source, to a short pulse-echo delay and to a high signal repetition rate. To test this hypothesis, three main electrophysiological experiments will be carried out under both free-field and closed-system stimulation conditions in order to study (1) the auditory spatial sensitivity and binaural properties of the pontine neurons; (2) echoranging properties of the pontine neurons and (3) encoding of signal repetition rate by the pontine neurons. A neural model and the specific procedures to test this model which underlies the formation of two possible types of excitatory-excitatory (EE) neurons in the pontine nuclei are proposed. Furthermore, procedures to explore the neural mechanisms underlying the formation of the best repetition rate encoded by each examined pontine neuron are also described. In auditory orientation, spatial sensitivity and sound localization are of primary importance to any animal. Since the bat relies essentially upon auditory signal processing for survival and its brain structure is fundamentally the same as other mammals including humans, it certainly provides the best model for studying neural mechanism underlying auditory perception. Thus, the results of these proposed studies will not only answer some specific questions regarding echolocation in bats but will also enhance the understanding of sound localization in humans.

Humans, and animals process auditory information carried by complex sounds so easily and so fast. This efficient signal processing is based on enormous computation taking place in the central auditory system. Auditory physiologists have explained that auditory signal processing or the response properties of central auditory neurons are resulted from divergent and convergent projections within the ascending auditory system. However, recent studies have shown that the corticofugal (descending) system plays a very important role in signal processing. It has been suggested that the corticofugal system regulates subcortical auditory signal processing through a highly focused positive feedback which works together with a wide spread lateral inhibition.
Using bats as a mammalian model system, this proposal will collect data from three hypothesis-driven experiments in order to form a hypothetical working model for corticofugal regulation of midbrain auditory information processing. These studies involve electrophysiology and iontophoresis under free field stimulation conditions. Specifically, this application will study (1) how corticofugal system may facilitate or inhibit auditory response properties of neurons in the external and central parts of a midbrain auditory nucleus (the inferior colliculus) (2) how neurons in these two parts of the inferior colliculus may interact during sound stimulation and (3) the possible neurotransmitters that may be involved in these auditory information transmissions.
The proposed study of the corticofugal system will contribute significantly to the development of a more realistic and dynamic model of central auditory signal processing. In particular, the data to be collected will help understand how the corticofugal system contributes to the optimization and reorganization of ascending auditory signal processing in subcortical auditory nucleus. This proposed study will advance our understanding of the functional role of the corticofugal system during central acoustic signal processing which has been given little attention until recently.