A principle aim of the field of neuroscience is the study of the mechanisms which enable learned complex behaviors, such as speaking or playing an instrument. However, the processes which underlie the generation of these behavioral sequences are poorly understood, in part because of the limitations of available methods for measuring neuronal activity in behaving animals. Recently, we designed and built a new experimental tool that enables the first ever intracellular recordings in freely behaving small animals engaged in complex behaviors. These recordings provide a wealth of information that is not available with extracellular recordings and allow for the testing of previously unapproachable hypotheses concerning the mechanisms of neural sequence generation in freely behaving animals. To that end, the experiments within this proposal focus on an important motor control nucleus in the zebra finch called HVC (formerly known as the high vocal center), which is analogous to motor areas of the mammalian neocortex. We have previously shown that HVC acts as a 'clock'for the production of learned vocalizations, but we understand little about the mechanisms by which this circuit operates. Experiments described in the first specific aim test the competing hypotheses that neurons within HVC are sequentially activated either through their intrinsic properties or through overt synaptic connections within that nucleus. The second specific aim will identify the relative impact of excitatory and inhibitory synaptic inputs on sequence generation. The third specific aim will directly address an existing controversy concerning the role of sensory feedback on motor patterning within HVC. Through these experiments, we will generate fundamental insights into the processes involved in the production of learned motor sequences in order to inform therapeutic approaches for a range of relevant disorders.
Vocal communication is an essential feature of human interaction, but the cellular and synaptic mechanisms that underlie speech production are poorly understood. Our experiments will focus on these issues using a newly designed experimental tool that will allow for the first ever intracellular view into the activity of single neurons during the production of learned vocalizations. These studies are likely to be relevant for understanding the mechanisms of a range of complex motor sequences and their pathologies.
|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|
|Long, Michael A; Lee, Albert K (2012) Intracellular recording in behaving animals. Curr Opin Neurobiol 22:34-44|
|Fee, Michale S; Long, Michael A (2011) New methods for localizing and manipulating neuronal dynamics in behaving animals. Curr Opin Neurobiol 21:693-700|