Human neonates use vision to guide behavior, form caregiver attachments, and build more complex visual and cognitive abilities. Defining the mechanisms by which vision comes 'online'in time for birth is thus essential to understand the development of normal and pathological visual processing. Visual perception requires the development of organized receptive fields as well as the development of cortical states that generate visual alertness and attention. Animal models have provided a mechanistic understanding of the former, but insight into the mechanisms by which alert visual response dynamics develop has been limited by a paucity of unanesthetized animal models with demonstrated homology to fetal and perinatal human cortical activity. To overcome this limitation, my collaborators and I have made a significant investment in the characterization of a behaving infant rat model that recapitulates early human cortical activity development. We propose to use this model to identify the network mechanisms that drive the development of cortical alertness, and characterize their role in the perinatal functional maturation of the visua response. In prior studies we identified a rapid maturation of visual cortical activity occurring 23 weeks before term (birth) in humans and 1-2 days before eye opening in rats. Before this switch cortical activity is dominated by network silence, interrupted by infrequent, large amplitude oscillatory bursts that occur both spontaneously and in response to light. The electrographic signature of alertness typical of the adult waking state, namely the """"""""activated"""""""" or """"""""desynchronized"""""""" state in the EEG, is not observed at these ages even when the infant is clearly awake. This period ends suddenly when oscillatory bursts are replaced by fast visual responses superimposed on an activated cortical state during wakefulness, which we call """"""""visual alertness"""""""". We will test the hypothesis the emergence of visual alertness is the result of rapid development of feed-forward cortical inhibition and a surge in norephinephrine (NE) release occurring just before eye opening. Our results will provide a novel understanding of how changing cortical network properties influence development of vision, and how ontogenetic control of the timing of these properties is achieved. We expect this information will inform the diagnosis and treatment of central visual and attention deficits prevalent in pre-term and other at risk infants.

Public Health Relevance

This work will reveal the mechanisms that ensure infants are capable of vision at birth. This is important because newborn infants use vision to learn about the world, construct finely tuned visual circuits, and direct appropriate behavioral responses to visual input. Because the timing of developmental milestones of cortical function is known to be disrupted in developmental disorders such as autism, attention deficit disorder, and schizophrenia, the identification of the neural mechanisms responsible for developmental timing and emergence of mature cortical function will be important for identification of likely pathogenic mechanisms and providing targets for future treatment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY022730-01A1
Application #
8579581
Study Section
Special Emphasis Panel (SPC)
Program Officer
Steinmetz, Michael A
Project Start
2013-09-01
Project End
2018-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$388,645
Indirect Cost
$138,645
Name
George Washington University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
043990498
City
Washington
State
DC
Country
United States
Zip Code
20052
Murata, Yasunobu; Colonnese, Matthew T (2018) Thalamus Controls Development and Expression of Arousal States in Visual Cortex. J Neurosci 38:8772-8786
Murata, Yasunobu; Colonnese, Matthew T (2018) Thalamic inhibitory circuits and network activity development. Brain Res :
Colonnese, Matthew T; Phillips, Marnie A (2018) Thalamocortical function in developing sensory circuits. Curr Opin Neurobiol 52:72-79
Colonnese, Matthew T; Shen, Jing; Murata, Yasunobu (2017) Uncorrelated Neural Firing in Mouse Visual Cortex during Spontaneous Retinal Waves. Front Cell Neurosci 11:289
Berzhanskaya, Julia; Phillips, Marnie A; Gorin, Alexis et al. (2017) Disrupted Cortical State Regulation in a Rat Model of Fragile X Syndrome. Cereb Cortex 27:1386-1400
Murata, Yasunobu; Colonnese, Matthew T (2016) An excitatory cortical feedback loop gates retinal wave transmission in rodent thalamus. Elife 5:
Shen, Jing; Colonnese, Matthew T (2016) Development of Activity in the Mouse Visual Cortex. J Neurosci 36:12259-12275
Berzhanskaya, Julia; Phillips, Marnie A; Shen, Jing et al. (2016) Sensory hypo-excitability in a rat model of fetal development in Fragile X Syndrome. Sci Rep 6:30769
Pelkey, Kenneth A; Barksdale, Elizabeth; Craig, Michael T et al. (2015) Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons. Neuron 85:1257-72
Colonnese, Matthew T (2014) Rapid developmental emergence of stable depolarization during wakefulness by inhibitory balancing of cortical network excitability. J Neurosci 34:5477-85