During different behavioral states, such as quiescence versus vigilance, neural circuits are set into distinct operating modes and respond to afferent inputs, such as sensory stimulation, in very different ways. In other words, neural circuits are rapidly configured into appropriate information processing modes demanded by behavioral states. The first question this project addresses is, what are the operating modes of sensorimotor circuits during different behavioral states and how are they set? During exploratory behaviors, animals move their body (head, limbs, and trunk) and adjust the position of the sensors (eyes, fingers, pinnae, whiskers) used to explore the environment. During these states, the brain must disambiguate the neural activity that causes the movements from the activity that is driven by the movement and its interaction with the environment. The second question this project addresses is, how does the brain differentiate motor from sensory activities during active exploration of the environment? As animals explore the environment, detection of an unexpected stimulus leads to an orienting response by which animals move to evaluate the stimulus. Repeated presentation of the stimulus without significant consequences leads to habitation of the orienting response, and the stimulus is eventually ignored. The third question this project addresses is, what neural circuits drive orienting responses and how does habituation occur at a neural level? Through association with other stimuli a detected sensory stimulus can acquire new meaning, and therefore be transformed into a conditioned stimulus. For instance, during active avoidance behavior, animals readily respond to a conditioned stimulus by shuttling to a different compartment of a cage in order to avoid a negative consequence. The last question this project addresses is, what neural circuits mediate active avoidance to a conditioned stimulus and how do these circuits operate at a synaptic/cellular level during this behavior? These questions will be investigated using a combination of methods that include electrophysiology, optogenetics, DREADDs, pharmacology, and histology applied using a variety of approaches ranging from acute slices of brain tissue to freely behaving rodents conducting behavioral tasks. We will take advantage of readily available Cre driver lines that allow to control the activity of specific neuronal populations and test their role in behavior. The neural and behavioral processes we study are normal, but when they go awry they lead to neurological and psychiatric disorders. Deciphering the normal operating modes of neural circuits is essential to understand how these operations are impacted by neurological and psychiatric disorders.

Public Health Relevance

The goal of this research is to determine the operating modes of sensorimotor circuits during the detection and processing of sensory stimuli, and how these circuits mediate appropriate orienting responses to novel stimuli and approach/escape/avoidance responses to meaningful stimuli. Such basic knowledge is vital to understand how the brain mediates normal behavior and has direct relevance to many neurological and psychiatric disorders, such as sensory neglect syndromes, learning disabilities, Parkinson's, autism, anxiety disorders, and others.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Unknown (R35)
Project #
1R35NS097272-01
Application #
9155936
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Gnadt, James W
Project Start
2016-12-01
Project End
2024-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Drexel University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19102