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Testing the effects of cortical disconnection in non-human primates  

To respond to the external environment, nerve cells signal to each other in intricate and stereotypical patterns using circuits that carry information from one region of the brain to another. Richard Krauzlis and his colleagues at the Salk Institute for Biological Studies are exploring how abnormal patterns of brain wiring can lead to the behaviors associated with autism spectrum disorders. People with autism have unusual and sometimes detrimental responses to their environment, such as not responding to social cues or an inordinate fear of the unfamiliar. These behaviors appear to result from an atypical visual alertness, such as noticing some stimuli but not others, and a different way of interpreting spatial information. These behaviors point to two particular regions of the brain known to control actions and attention to the surroundings — the frontal cortex and the parietal lobe, respectively — and suggest that the connections between these two areas are not properly formed in the brains of people with autism. Krauzlis and colleagues plan to test this hypothesis by interrupting the circuits between the two regions using a new technique they call 'selective disconnection.' They plan to infect the neurons with a virus carrying the fruit fly allostatin receptor that is taken up by synapses and then transported backwards through the axons to the cell body. Injecting the virus in the frontal cortex would selectively infect neurons in the parietal cortex that project to the frontal cortex or vice versa. When the researchers then inject the receptor's ligand, allostatin, into the parietal cortex, the ligand would selectively inactivate the circuit connection from the parietal cortex to the frontal cortex. The researchers also plan to use classical techniques to non-selectively inactivate neurons locally in the brain. By associating specific lesions with autistic behaviors, the researchers hope to develop a functional map of the region that may indicate which particular pathways are involved in autism. The researchers also plan to evaluate how the autistic brain chooses what to pay attention to. For instance, given two objects, which does a person with autism follow and how does that decision vary when a reward is associated with one object or if the surrounding environment changes? Then, Krauzlis and his team hope to associate particular neural connections with those thought processes. This work could also offer new insights on the phenotypic diversity of the disorder. Krauzlis suggests that the distinct set of abilities and disabilities seen in different people with autism may arise from unique patterns of neuron projections in their brains. Project Status


Funder Simons Foundation
Fiscal Year Funding $75,000.00
Current Award Period 2008-2010
Project Number 95234
Principal Investigator Krauzlis, Richard
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Neural Systems
Strategic Plan Objective 2O. Not specific to Question 2 objectives
Federal or Private? Private
Institution The Salk Institute for Biological Studies
State/Country California
Web Link 1 Testing the effects of cortical disconnection in non-human primates (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects Testing the effects of cortical disconnection in non-human primates | $150,000.00 | 2008 | Project number unavailable
Testing the effects of cortical disconnection in non-human primates | $150,000.00 | 2009 | 95234