Robert C. Froemke, PhD
Assistant Professor of Physiology and Neuroscience
Ph.D., 2004 University of California, Berkeley
New York University School of Medicine
540 First Avenue, Floor 5, Room 9
New York, NY 10016
Tel: (212) 263-4082
Fax: (212) 263-7760
Lab Website: http://saturn.med.nyu.edu/research/mn/froemkelab
Research Theme(s): Developmental Neurobiology, Neuronal Plasticity, Sensory Systems
Keywords: Neuroscience, Physiology, Brain Repair, Plasticity
New synapses for old brains: functional integration of precursor cells into extant tissue
Transplantation of stem cells or progenitor cells into host tissue may be a promising method for repairing aged, damaged, or diseased organs. This is especially true for neural circuits of the cerebral cortex, which are believed to lack endogenous neural stem cells of their own in adult humans. Brain damage that occurs after stroke, chronic epilepsy, or in Alzheimers and Parkinsons patients may be reversible after cell transplantation, but knowledge of how cellular grafts interact with and affect native tissues is sorely lacking.
We study the efficacy of interneuron progenitor cell transplants for brain repair in rodent models. In collaboration with Arturo Alvarez-Bullya, Sunil Gandhi, and Derek Southwell (members of the Institute for Regenerative Medicine at the University of California, San Francisco), we have discovered that transplantation of tissue from the embryonic medial ganglionic eminence- a main source of interneuron precursors for the developing cerebral cortex (Corbin et al. 2001, Nat. Neurosci. 4:1177)- leads to functional integration of these new cells into recipient neural networks. Compared to young brains, neural circuits in older animals are normally less plastic, i.e., have less capacity to change, to be modified by sensory experience, and to withstand and recover from injury or disruptive episodes. However, transplantation of embryonic progenitor cells rejuvenates the cortex, and opens a new period of heightened neuroplasticity in adult animals (Southwell et al. 2010, Science 327:1145).
We currently use a combination of methods, including electrophysiology (recording from pairs of native and transplanted cells), molecular biology and pharmacology (to disrupt or induce specific signaling pathways or gene expression), and computational approaches to ask two main questions related to the incorporation of new neurons into extant circuitry.
First, how many new cells can be supported by the existing tissue? After overloading the adult cortex with many more interneuron precursors, the majority of these new cells are culled within several days, although a large fraction is maintained indefinitely. We aim to determine what factors and activity patterns allow certain progenitor cells to fully and persistently integrate into the rest of the cortex, while other cells do not survive.
Second, how does the addition of new interneurons, which are usually inhibitory cells, promote plasticity within neural networks? We hypothesize that a switch from a smaller number of relatively strong synapses (before transplantation) to a larger number of relatively weak synapses (as we discovered after transplantation) is critical, keeping the total synaptic drive relatively constant, while making it much easier for any one particular synapse to be changed by variations in sensory experience.
A future project will involve testing the effects of interneuron transplantation in behaving animals, to ask whether such cell grafts can directly enhance sensory perception (particularly in aged animals with degraded sensory representations), or might lead to gains in task performance.
- Spectrotemporal dynamics of auditory cortical synaptic receptive field plasticity. Froemke RC, Martins AR. Hear Res. 2011 Sep;279(1-2):149-61. Epub 2011 Mar 21. PMID: 21426927
- Development of auditory cortical synaptic receptive fields. Froemke RC, Jones BJ. Neurosci Biobehav Rev. 2011 Nov;35(10):2105-13. Epub 2011 Feb 15. PMID: 21329722
- Developmental sensory experience balances cortical excitation and inhibition. Dorrn, A.L., Yuan, K., Barker, A.J., Schreiner, C.E., and Froemke, R.C. (2010). Nature 465, 932-936. PMID: 20559387
- Cortical plasticity induced by inhibitory neuron transplantation. Southwell, D.G., Froemke, R.C., Alvarez-Buylla, A., Stryker, M.P., and Gandhi, S.P. (2010). Science 327, 1145-1148. PMID: 20185728
- Requirement of an allosteric kinetics of NMDA receptors for spike timing-dependent plasticity. Urakubo, H., Honda, M., Froemke, R.C., and Kuroda, S. (2008). Journal of Neuroscience 28, 3310-3323. PMID: 18367598
- A synaptic memory trace for cortical receptive field plasticity. Froemke, R.C., Merzenich, M.M., and Schreiner, C.E. (2007). Nature 450, 425-429. PMID: 18004384
- Perinatal exposure to a non-coplanar PCB alters tonotopy, receptive fields and plasticity in rat primary auditory cortex. Kenet, T., Froemke, R.C., Schreiner, C.E., Pessah, I.N., and Merzenich, M.M. (2007). Proceedings of the National Academy of Science USA 104, 7646-7651. PMID: 17460041