Understanding the cellular mechanisms that underlie attention is crucial for developing effective treatments for the many psychiatric and learning disorders that affect attention. We have developed experimental protocols in the barn owl that allow us to study the cellular basis of a fundamental component of attention, stimulus selection, in quantitative detail.
The aim of the proposed research is to analyze characteristics of bottom-up (automatic) and top-down stimulus selection at the neuronal level and to elucidate mechanisms that underlie these processes. The properties of bottom-up and top-down stimulus selection will be studied in the optic tectum, a structure known to be involved in spatial attention. The effects of multiple, simultaneous sensory stimuli on neuronal responses will be measured as the salience and location of competing stimuli are varied parametrically. Top-down signals (originating in the forebrain) that bias stimulus selection will be activated by electrical microstimulation. Finally, the respective roles of specialized cholinergic and GABAergic nuclei in bottom-up and top-down stimulus selection will be explored with electrophysiology and pharmacological inactivation experiments. The mechanisms by which the brain selects stimuli for attention are not known. In addition, the effects of cholinergic input on information processing in the brain are not understood. Many debilitating conditions (e.g., Schizophrenia, Autism, ADHD) include dysfunctions of stimulus selection, and others (e.g., Alzheimer's, Parkinson's, Down's) are associated with dysregulation of cholinergic transmission. An understanding of the cellular mechanisms of stimulus selection and the function of cholinergic circuits is crucial for developing treatments that can mitigate or remediate the devastating effects of these conditions.

Public Health Relevance

Many debilitating, psychiatric conditions (such as Schizophrenia, Autism and Attention Disorder) include dysfunctions of attention, and others (such as Alzheimer's, Parkinson's and Down's Syndrome) are associated with dysregulation of cholinergic circuitry in the brain. The proposed research will explore the cellular mechanisms of attention and the functional properties of cholinergic circuits. The results from this research will provide crucial information that may help in the development of treatments that can mitigate or remediate the devastating effects of these psychiatric conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY019179-33S1
Application #
8704650
Study Section
Program Officer
Steinmetz, Michael A
Project Start
2013-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
33
Fiscal Year
2013
Total Cost
$40,525
Indirect Cost
$16,909
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Goddard, C Alex; Huguenard, John; Knudsen, Eric (2014) Parallel midbrain microcircuits perform independent temporal transformations. J Neurosci 34:8130-8
Mysore, Shreesh P; Knudsen, Eric I (2014) Descending control of neural bias and selectivity in a spatial attention network: rules and mechanisms. Neuron 84:214-26
Mysore, Shreesh P; Knudsen, Eric I (2013) A shared inhibitory circuit for both exogenous and endogenous control of stimulus selection. Nat Neurosci 16:473-8
Goddard, C Alex; Sridharan, Devarajan; Huguenard, John R et al. (2012) Gamma oscillations are generated locally in an attention-related midbrain network. Neuron 73:567-80
Mysore, Shreesh P; Knudsen, Eric I (2012) Reciprocal inhibition of inhibition: a circuit motif for flexible categorization in stimulus selection. Neuron 73:193-205
Knudsen, Eric I (2011) Control from below: the role of a midbrain network in spatial attention. Eur J Neurosci 33:1961-72
Mysore, Shreesh P; Asadollahi, Ali; Knudsen, Eric I (2011) Signaling of the strongest stimulus in the owl optic tectum. J Neurosci 31:5186-96
Mysore, Shreesh P; Knudsen, Eric I (2011) The role of a midbrain network in competitive stimulus selection. Curr Opin Neurobiol 21:653-60
Asadollahi, Ali; Mysore, Shreesh P; Knudsen, Eric I (2011) Rules of competitive stimulus selection in a cholinergic isthmic nucleus of the owl midbrain. J Neurosci 31:6088-97

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