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? 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 disorders. Deciphering the normal operating modes of neural circuits is essential to understand how these operations are impacted by neurological 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 or 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 disorders, and others.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Unknown (R35)
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Special Emphasis Panel (ZNS1)
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Gnadt, James W
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Drexel University
Anatomy/Cell Biology
Schools of Medicine
United States
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Castro-Alamancos, Manuel A; Favero, Morgana (2016) Whisker-related afferents in superior colliculus. J Neurophysiol 115:2265-79
Hormigo, Sebastian; Vega-Flores, German; Castro-Alamancos, Manuel A (2016) Basal Ganglia Output Controls Active Avoidance Behavior. J Neurosci 36:10274-10284
Castro-Alamancos, Manuel A; Favero, Morgana (2015) NMDA receptors are the basis for persistent network activity in neocortex slices. J Neurophysiol 113:3816-26
Castro-Alamancos, Manuel A; Bezdudnaya, Tatiana (2015) Modulation of artificial whisking related signals in barrel cortex. J Neurophysiol 113:1287-301
Castro-Alamancos, Manuel A; Gulati, Tanuj (2014) Neuromodulators produce distinct activated states in neocortex. J Neurosci 34:12353-67
Bezdudnaya, Tatiana; Castro-Alamancos, Manuel A (2014) Neuromodulation of whisking related neural activity in superior colliculus. J Neurosci 34:7683-95
Castro-Alamancos, Manuel A (2013) The motor cortex: a network tuned to 7-14 Hz. Front Neural Circuits 7:21
Favero, Morgana; Castro-Alamancos, Manuel A (2013) Synaptic cooperativity regulates persistent network activity in neocortex. J Neurosci 33:3151-63
Favero, Morgana; Varghese, Gladis; Castro-Alamancos, Manuel A (2012) The state of somatosensory cortex during neuromodulation. J Neurophysiol 108:1010-24
Hirata, Akio; Castro-Alamancos, Manuel A (2011) Effects of cortical activation on sensory responses in barrel cortex. J Neurophysiol 105:1495-505

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