Results Through Rehabilitation & Research
Associate Professor, Neurology and Neuroscience
Weill Cornell Medical College
The progression of Parkinson’s disease (PD) is associated with the loss of neurons in a specific area of the brain called the substantia nigra. The neurons lost in PD use dopamine as their neurotransmitter and are required for normal movement control. Dopamine is also found in neurons in other areas of the brain, including the olfactory bulb. My laboratory is interested in the dopamine producing neurons of the olfactory system.
At one time it was thought that neurons were only produced during gestation but these neurons are even generated in adults, from stem cells. The olfactory system may be a possible source of stem cells that can be used to replace the damaged neurons. Understanding where these neurons arise, the signals involved in determining the pathway by which these cells migrate to their proper location, and why only some of the cells become dopamine neurons are among the questions we are studying.
My laboratory uses a number of model systems to study the dopamine neurons. One of these systems uses mice that express a green fluorescent protein in the dopamine neurons, allowing us to follow their migration. Dopamine synthesis in the olfactory bulb is also regulated by odor stimulation. To study the molecular mechanisms underlying dopamine biosynthesis, we use a model in which access of odor molecules to the nose is blocked.
Our long-term goals are to determine if there is a unique olfactory stem cell that produces interneurons with a dopamine phenotype, to determine how it becomes a dopamine neuron, and to discover the mechanisms regulating dopamine synthesis in the mature neuron. The answers may lead to replacement of the dopamine-producing neurons that are destroyed in Parkinson’s and other neurodegenerative diseases.
Wells College - Aurora, NY. (1963)
University of Illinois, Medical Center (1967)
University of Iowa (1976)
Post Doctoral Fellow
Cornell University Medical College, Neuroscience (1976-78)
Weill Cornell Medical College (1994)
Cave JW, Baker H (In press) Adult Neurogenesis in the SVZ and Migration to the Olfactory Bulb. In Handbook of Olfaction and Gustation. R Doty (Ed). New York, NY: Marcel Dekker.
Banerjee K, Akiba Y, Baker H, Cave JW. Epigenetic control of neurotransmitter expression in olfactory bulb interneurons. Int J Dev Neurosci. 2013 Oct;31(6):415-23. doi: 10.1016/j.ijdevneu.2012.11.009. Epub 2012 Dec 3.
Cave JW, Banerjee K, Baker H (2012) Species-specific molecular mechanisms establishing the dopamine neuronal phenotype. In Dopamine: Functions, Regulation and Health Effects. E Kudo & Y Fujii (Eds).Happauge, NY: Nova Science Publishers.
Cave JW, Akiba Y, Banerjee K, Bhosle S, Berlin R and Baker H (2010) Differential regulation of dopaminergic gene expression by Er81. J. Neurosci. 30:4717-4724. PMC2859884.
Akiba Y, Cave JW, Akiba N, Langley B, Ratan RR and Baker H (2010) Histone deacetylase inhibitors de-repress tyrosine hydroxylase expression in the olfactory bulb and rostral migratory stream. Biochem Biophys Res Commun. 303:673-677. PMC2848448.
Cave JW and Baker H (2009). Dopamine systems in the forebrain. Adv Exp Med Biol. 651, 15-35. PMC2779115.
Akiba Y, Sasaki H, Huerta PT, Estevez AG, Baker H and Cave JW. (2009). gamma-Aminobutyric acid-mediated regulation of the activity-dependent olfactory bulb dopaminergic phenotype. J Neurosci Res. 87(10), 2211-2221. PMC2765820.
Akiba N, Jo S, Akiba Y, Baker H, and Cave JW (2009). Expression of EGR-1 in a subset of olfactory bulb dopaminergic cells. J Mol Histol. 40(2), 151-155. PMC2765800.
Akiba Y, Sasaki H, Saino-Saito S and Baker H (2007). Temporal and spatial disparity in cFOS expression and dopamine phenotypic differentiation in the neonatal mouse olfactory bulb. Neurochem Res, 32(4-5), 625-634.
Saino-Saito S, Cave JW, Akiba Y, Sasaki H, Goto K, Kobayashi K, Berlin R, and Baker H. (2007) ER81 and CaMKIV identify anatomically and phenotypically defined subsets of mouse olfactory bulb interneurons. J. Comp. Neurol, 502, 485-596.
From where and when do dopamine neurons develop in the olfactory bulb? This seemingly mundane question becomes fascinating when one considers the fact that these neurons are born from mid-gestation to death. Even in the adult, new neurons are generated in the wall of the lateral ventricle and migrate in the rostral migratory stream to the olfactory bulb.
What are the molecular mechanisms that are required for determination of the dopamine phenotype? We have shown that the ETS transcription factor is involved in generation of the dopamine phenotype in most of the neurons.
How do the dopamine and other neurons integrate into circuits?
Does generation and integration require activity? Perturbations that interrupt sensory afferent innervations of the olfactory bulb results in a loss of expression of tyrosine hydroxylase, the first enzyme in the dopamine biosynthetic pathway. This enzyme serves as a marker for the dopamine neurons.
What are the molecular signals involved in dopamine neuron generation, migration and integration into appropriate neural circuits?
Plasticity in the Aging Olfactory System, NIDCD 1 R01 DC008955