This project aims to investigate the circuit mechanisms that enable learned complex behaviors, such as playing the violin or hitting a tennis forehand. At present, the processes which underlie the generation of these behavioral sequences by neural networks are poorly understood. Specifically, the contributions of various cell types to this network behavior remain underexplored. Here we consider an important motor control nucleus in the zebra finch called HVC (formerly known as the high vocal center), which produces neural sequences during the performance of the learned courtship song. Our proposal focuses on local circuit interneurons, which represent the sole source of inhibition to this network. Several models have been proposed to explain the role of inhibition in song production, but consensus remains elusive. To test these models, we propose a series of electrophysiological, imaging, and optogenetic studies that will enable us to manipulate and monitor HVC interneurons selectively, often in the context of song production.
In Aim 1, we will examine the role of inhibition from a postsynaptic perspective. The primary focus of this aim is to record inhibitory synaptic currents onto HVC projection neurons during song production.
In Aim 2, we will examine the role of inhibition from a presynaptic perspective by directly measuring populations of identified interneurons during singing. We will also gauge the impact of individual interneurons on the network using anatomical and electrophysiological methods.
In Aim 3, we will use in vivo and in vitro measurements to characterize the genetic subtypes of HVC interneurons and to distinguish their roles within the network.

Public Health Relevance

The proposed project is relevant to public health because understanding how forebrain circuits enable behavior sequences will help to illuminate the processes underlying the acquisition and performance of skilled movements. Thus, this research is relevant to the NIH's mission to contribute to the body of knowledge needed to develop novel therapies for treating those who experience motor disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS075044-08
Application #
9936255
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
2011-09-30
Project End
2022-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
8
Fiscal Year
2020
Total Cost
Indirect Cost
Name
New York University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Benezra, Sam E; Narayanan, Rajeevan T; Egger, Robert et al. (2018) Morphological characterization of HVC projection neurons in the zebra finch (Taeniopygia guttata). J Comp Neurol 526:1673-1689
Katlowitz, Kalman A; Picardo, Michel A; Long, Michael A (2018) Stable Sequential Activity Underlying the Maintenance of a Precisely Executed Skilled Behavior. Neuron 98:1133-1140.e3
Kornfeld, Jörgen; Benezra, Sam E; Narayanan, Rajeevan T et al. (2017) EM connectomics reveals axonal target variation in a sequence-generating network. Elife 6:
Katlowitz, Kalman A; Oya, Hiroyuki; Howard 3rd, Matthew A et al. (2017) Paradoxical vocal changes in a trained singer by focally cooling the right superior temporal gyrus. Cortex 89:111-119
Picardo, Michel A; Merel, Josh; Katlowitz, Kalman A et al. (2016) Population-Level Representation of a Temporal Sequence Underlying Song Production in the Zebra Finch. Neuron 90:866-76
Long, Michael A; Katlowitz, Kalman A; Svirsky, Mario A et al. (2016) Functional Segregation of Cortical Regions Underlying Speech Timing and Articulation. Neuron 89:1187-1193
Vallentin, Daniela; Kosche, Georg; Lipkind, Dina et al. (2016) Neural circuits. Inhibition protects acquired song segments during vocal learning in zebra finches. Science 351:267-71
Kosche, Georg; Vallentin, Daniela; Long, Michael A (2015) Interplay of inhibition and excitation shapes a premotor neural sequence. J Neurosci 35:1217-27
Vallentin, Daniela; Long, Michael A (2015) Motor origin of precise synaptic inputs onto forebrain neurons driving a skilled behavior. J Neurosci 35:299-307
English, Daniel F; Peyrache, Adrien; Stark, Eran et al. (2014) Excitation and inhibition compete to control spiking during hippocampal ripples: intracellular study in behaving mice. J Neurosci 34:16509-17

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