1985 — 1988 |
Oliver, Douglas L [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Synaptic Organization of Auditory System @ University of Connecticut Sch of Med/Dnt
This project is designed to investigate the structural basis for auditory information processing in the inferior colliculus (IC). The proposed experiments focus on the individual components of the synaptic organization which are: 1) the synaptic contacts formed by afferent axons from the brainstem and neocortex in the IC; 2) the intrinsic circuitry in the IC; and 3) the neurons of the IC whose structure and innervation integrate these inputs to produce responses to auditory signals. In the proposed experiments we will use light (LM) and electron microscopic (EM) techniques to: 1. Identify the synaptic features of brainstem afferent pathways and relate them to binaural interactions in the IC. This includes experiments to: a) Establish the bilateral convergence of cochlear nucleus afferents on single IC neurons with axonal transport and degeneration techniques at the LM and EM level. b) Demonstrate directly the postsynaptic termination of cochlear nucleus afferents on specific cell types in the IC with Golgi-EM and degeneration methods. c) Distinguish the morphology and synaptic contacts made by afferents from the superior olivary complex and dorsal nucleus of the lateral lemniscus. 2. Identify the types of intrinsic axons in the IC through EM analysis of HRP-injected and Golgi-impregnated axons and their endings. 3. Determine which axon types in the IC might use GABA as a transmitter by identifying those which preferentially accumulate 3H-GABA with EM autoradiographic methods. 4. Investigate the dendritic morphology and patterns of synaptic innervation of physiologically characterized, HRP-injected IC neurons with LM and EM techniques. 5. Identify the neocortical afferents to the IC with anterograde axonal transport and EM autoradiography methods.
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0.904 |
1989 — 2013 |
Oliver, Douglas L [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Synaptic Organization of the Auditory System @ University of Connecticut Sch of Med/Dnt
The inferior colliculus (IC) is a critical structure that integrates signals from the lower brainstem before projecting the information towards the auditory thalamus and cortex. We propose that functional zones in the IC may be created by specific combinations of inputs from brainstem sources. Aim 1 will use anatomical and physiological methods in the cat to identify functional zones in the IC based on three major excitatory inputs. We will test the hypothesis that ipsilateral projects from medial superior olive (MSO) and contralateral projects from the lateral SO (LSO) are anatomically segregated. We will show that the inputs from MSO and MSO and cochlear nucleus also define separate functional zones. Moreover, we will physiologically identify the functional zones related to MSO, LSO, and cochlear nucleus inputs. Aim 2 will identify functional zones in the IC based on the integration of excitatory and inhibitory inputs. Inhibitory inputs to the IC create inhibitory side bands and transform the response to interaural time differences (ITD). Major sources of inhibitory inputs are the dorsal nucleus of the lateral lemniscus (DNLL), the ipsilateral project from LSO, and local inhibitory IC neurons. We will test the hypothesis that the projections from the ipsilateral MSO and the contralateral DNLL have a common target in the IC. We will also show that the inputs from the contralateral DNLL and ipsilateral LSO do not converge. We will identify local circuit neurons in the IC. Finally, we will test the hypothesis that some ITD responses in IC will be altered by suppression of DNLL or inhibitory local IC inputs. In aim 3, we will identify functional cell types in the IC. We will show that the combination of K+ channels or their subcellular localization are related to cell type and GABA content in the IC. Finally, we will demonstrate that neurons with different firing patterns and whole-cell currents are related to different patterns of K+ channel and/or GABA expression.
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0.904 |
1996 — 1997 |
Oliver, Douglas L [⬀] |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Structure and Function of Parallel Auditory Pathways @ University of Connecticut Sch of Med/Dnt
This project will address the organization of neurons into parallel pathways within the central auditory system. While the anatomical evidence for parallel circuitry in the auditory system is compelling, the functional consequences of this circuitry are not known. This study will elucidate the role of this circuitry in central auditory processing. Neurons in the auditory system can be classified according to their binaural response properties. Monaural neurons respond only to sounds presented in one ear. Binaural neurons can be effected by sounds delivered to both ears. Both types of neuron may be involved in a variety of auditory functions, but some behaviors, like sound localization, may emphasize one class of neuron over another. Monaural and binaural neurons can be found at all levels of the auditory system, but, the anatomical cell types and circuits related to these responses are not certain. We hypothesize that cells which respond only to monaural stimulation are synaptically connected to form one or more monaural circuits. These monaural circuits would be distinct from circuits concerned with binaural processing. In the present proposal, we will focus on the neurons with monaural response features in the lower brain stem. The cochlear nucleus (CN) and ventral nucleus of the lateral lemniscus (VNLL) are major centers with monaural neurons, and both project to the inferior colliculus (IC). Despite the importance of these structures for understanding monaural responses in the IC and in higher centers, critical data are still lacking on the cells involved in these projections. Therefore, AIM 1 is to determine which cell types participate in the CN-VNLL-IC circuit and compare them to the cells involved in the CN-IC circuit. Axonal transport labeling in vivo and intracellular injections in fixed brain slices will be used. We predict that different cell types will participate in each circuit. Double-labeling experiments will determine if the same neurons in the CN project to both the VNLL and IC. Finally, anterograde transport and intracellular experiments will determine the nature of the synaptic connections made in the VNLL by axons from the CN. We anticipate that specific synaptic arrangements will characterize the neuropil of the VNLL. The monaural responses in VNLL are attributed to strong inputs from the contralateral CN and a dearth of inputs from the superior olivary complex. There is little physiological data on the VNLL to confirm its monaural properties in terrestrial mammals. Therefore, AIM 2 is to characterize the response properties of units in the VNLL of the awake rabbit. We anticipate that most cells in VNLL will be monaural; however, their responses may be different from those in the CN.
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0.904 |
2015 — 2016 |
Oliver, Douglas L [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Synaptic Plasticity in the Inferior Colliculus @ University of Connecticut Sch of Med/Dnt
DESCRIPTION (provided by applicant): Our overall goal is to understand how activity may alter auditory signal processing in the inferior colliculus (IC), a critical auditory center in the midbrain. As the midbrain hub of the auditory pathway, the neurons in the central nucleus of the IC integrate different types of ascending auditory information. The IC also gates the information reaching the auditory cortex through direct excitation and direct inhibition of the medial geniculate body. The unique position of IC has made it a recent target for deep brain stimulation. However, little is known about how evoked activity, either acoustic or electrical, may alter information transmission in IC neurons. Synaptic inputs are critical in shaping the responses of IC neurons to sound. In the central nervous system, it is well known that the synapses may be modified, e.g. potentiated or depressed in an activity dependent manner. Synaptic plasticity may play an important role for learning & memory and the development of neural circuits. Although long term potentiation (LTP) and depression (LTD) exist in the IC, their role is unclear. They might shape the neuronal responses to sound based on recent activity in the auditory pathway in adults. One critical factor in synaptic plasticity is the relative timing between the pre- and post- spike activity. Spike Timing Dependent Plasticity (STDP) is a formal way of evaluating that relationship often inducing both LTP and LTD in the same neuron when a different temporal order is used. Our project will elucidate the character of STDP in the IC. Since both sound processing and STDP phenomena vary temporally in the same millisecond time range, STDP may be highly relevant for the synaptic processing of sound. Moreover, a distinct advantage of using STDP in the experimental study of synaptic plasticity is that the location of the plasticity is clear and is restricted to the pre- and/or post synaptic sites of the recorded neuron in the IC. Our main goal is to investigate how activity may change the sound evoked responses in the inferior colliculus in mice in vivo. For this purpose, we will record sound-evoked neural responses with either juxtacellular/cell-attached or whole cell in vivo recording techniques. We will use STDP to compare the response to sound before and after the neuron is trained by combining the sound evoked response with action potentials evoked by single-cell current injection (nano-stimulation). Separate experiments will investigate the effects of STDP on spectral (frequency) tuning to sound, temporal modulation of sound relevant for communication, and responses to binaural stimuli relevant to sound localization. In complementary experiments, we will use a brains slice preparation of IC to investigate whether STDP is the same in different neuron types. Specifically, we will test GABAergic and glutamatergic neurons in GAD67-GFP transgenic mice where GABAergic neurons are labeled. Generally, the IC and lower auditory centers are considered less 'plastic' than auditory cortex. Our project may change this view and reveal physiologically relevant activity-dependent changes in IC. Such knowledge may be essential to understand normal hearing and for therapy, training, rehabilitation after hearing loss.
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0.904 |