Development of hemodynamic responses and functional connectivity in rat somatosensory cortex

Abstract

Functional magnetic resonance imaging (fMRI) is a valuable method for probing postnatal circuit refinement and plasticity. However, its use during early development has been hindered by uncertainty as to the nature of neurovascular coupling in young individuals. Here we used somatosensory stimulation in rats to determine age-related parameters of the blood oxygenation level–dependent (BOLD) signal from its apparent inception on postnatal day 13 to adulthood. By comparing fMRI measurements with electrophysiological recordings, we determined that the regional BOLD response in these animals undergoes a systematic decline in latency and growth in amplitude over this period. We found no evidence of negative BOLD at any age. Maturation of hemodynamic responses correlated with age-dependent increases in susceptibility to inhibition of carbonic anhydrase. With knowledge of the infant BOLD response characteristics, we showed that interhemispheric and higher-order cortical stimulus responses are enhanced during the first several weeks after birth.

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Figure 1: Age-dependent trends in BOLD fMRI responses to forepaw stimulation in isoflurane-anesthetized rats.
Figure 2: Changing neuronal and hemodynamic responses during development.
Figure 3: Carbonic anhydrase activity correlates with the development of BOLD hemodynamics.
Figure 4: Development of the forepaw representation in primary and secondary somatosensory cortex.

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Acknowledgements

We thank John Marota, George Dai and Joseph Mandeville. We would also like to thank David Cory for the use of the magnet and for technical advice. The authors received generous support from the McGovern Institute for Brain Research and the Whitehead Institute for Biomedical Research, where A.J. was a Whitehead Fellow. K.K. is a member of the Nordic Center of Excellence for Research in Water Imbalance Related Disorders. Some preliminary data for this study was generated with additional support to A.J. from the Martinos Center for Biomedical Imaging at the Massachusetts General Hospital.

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The research was designed, carried out, analyzed and written by M.T.C. and A.J. M.C.-P. initiated the project. K.K. suggested and consulted on the carbonic anhydrase experiments. M.A.P. designed and carried out the blood carbonic anhydrase assays.

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Correspondence to Matthew T Colonnese.

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Colonnese, M., Phillips, M., Constantine-Paton, M. et al. Development of hemodynamic responses and functional connectivity in rat somatosensory cortex. Nat Neurosci 11, 72–79 (2008). https://doi.org/10.1038/nn2017

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