Michael Bubser, Ph.D.

Assistant Research Professor

     M.S.    University of Stuttgart, Stuttgart, Germany, 1987
     Ph.D.   University of Stuttgart, Stuttgart, Germany, 1992

 

Biosketch and Research Interests

Michael Bubser, Ph.D. is a Research Instructor who joined the Conn laboratory in July 2009. Doug obtained his doctoral training in the laboratory of Werner J. Schmidt, Ph.D. at the University of Stuttgart in Germany. His graduate studies focused on the behavioural pharmacology of the dopaminergic innervations of the prefrontal cortex of the rat. He also examined the role of competitive and non-competitive antagonists of the N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors in animal models of Parkinson’s disease and schizophrenia as well as their impact on dopamine neurochemistry. During his stay at the Netherlands Institute for Brain Research in Amsterdam (The Netherlands) he got intrigued by the possibilities that functional anatomical techniques could contribute to unraveling the interaction of complex brain circuitry. During his work with Ariel Y. Deutch in the Departments of Psychiatry at Yale University and Vanderbilt University he continued his functional anatomical studies by examining sites and mechanism(s) of action of typical and atypical antipsychotic drugs (APD) and psychostimulants. In particular he investigated novel sites of APD actions in the diencephalon and demonstrated that there is a correlation between the activation of orexin neurons in the lateral hypothamus and the liability of certain APDs to cause significant weight gain.

When he joined the Conn laboratory he started applying his knowledge in functional neuroanatomy and behavioural pharmacology to the study of G-protein-coupled receptors (GPCRs). He currently works on characterizing the therapeutic potential of positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 4 (mGluR4) in animal models of Parkinson’s disease. A second avenue of his research is the study of in vivo actions of muscarinic cholinergic receptor ligands, in particular M1 and M4 PAMs.

 

Selected Publications

Schmidt WJ, Bubser, M. Anticataleptic effects of the N-methyl-D-aspartate antagonist MK_801 in rats. Pharmacol Biochem Behav 1989; 32:621-623.

Bubser M, Schmidt WJ 6-hydroxydopamine lesion of the rat prefrontal cortex increases locomotor activity, impairs acquisition of delayed alternation tasks but does not affect uninterrupted maze tasks. Behav. Brain Res 1990; 37:157-168.

Bubser M, Keseberg U, Notz PK, Schmidt, WJ. Differential behavioural and neurochemical effects of competitive and non-competitive NMDA receptor antagonists in rats. Eur J Pharmacol 1992; 229:75-82.

Bubser M, Koch M. Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex. Psychopharmacology 1994; 113:487-492.

Koch M, Bubser M. Deficient sensorimotor gating after 6-hydroxydopamine lesion of the rat medial prefrontal cortex is reversed by haloperidol. Eur J Neurosci 1994; 6:1837-1845.

Bubser M, Zadow B, Kronthaler UO, Felsheim U, Rückert NGH, Schmidt WJ Behavioural pharmacology of the non-competitive NMDA antagonists dextrorphan and ADCI: relations between locomotor stimulation, anticataleptic potential and forebrain dopamine metabolism. Naunyn-Schmiedeberg’s Arch Pharmacol 1997; 355:767-773.

Bubser M, de Brabander JM, Timmerman W, Feenstra MGP, Erdtsieck-Ernste EBHW, Rinkens A, van Uum JFM, Westerink BHC. Disinhibition of the mediodorsal thalamus induces Fos-like immunoreactivity in both pyramidal and GABA-containing neurons in the medial prefrontal cortex of rats, but does not affect prefrontal extracellular GABA levels. Synapse 1998; 30:156-165.

Bubser M, Deutch AY. Stress induces Fos expression in neurons of the thalamic paraventricular nucleus that innervate limbic forebrain sites. Synapse 1999; 32:13-22.

Bubser M, Scruggs JL, Young CD, Deutch AY. The distribution and origin of the calretinin-containing innervation of the nucleus accumbens of the rat. Eur J Neurosci 2000; 12:1591-1598.

Bubser M, Backstrom JR, Sanders-Bush E, Roth BL, Deutch AY. Distribution of serotonin 5-HT2A receptors in afferents of the rat striatum. Synapse 2001; 39:297-304.

Bubser M, Deutch AY. Differential effects of typical and atypical antipsychotic drugs on striosome and matrix compartments of the striatum. Eur J Neurosci 2002; 15:713-720.

Fadel J, Bubser M, Deutch AY. Differential activation of orexin neurons by antipsychotic drugs associated with weight gain. J Neurosci 2002; 22: 6742-6746.

Bubser M, Fadel JR, Jackson LL, Meador-Woodruff JH, Jing D, Deutch AY. Dopaminergic regulation of orexin neurons. Eur J Neurosci 2005; 11: 2993-3001.

Jones CK, Brady AE, Davis AA, Xiang Z, Bubser M, Tantawy MN, Kane AS, Bridges TM, Kennedy JP, Bradley SR, Peterson TE, Ansari MS, Baldwin RM, Kessler RM, Deutch AY, Lah JJ, Levey AI, Lindsley CW, Conn PJ. Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic_like activity in rats. J Neurosci 2008; 28:10422-10433

Nayyar T, Bubser M, Ferguson MC, Neely MD, Goodwin JS, Montine TJ, Deutch AY, Ansah TA. Cortical serotonin and norepinephrine denervation in parkinsonism: Preferential loss of the beaded serotonin innervation. Eur J Neurosci 2009; 30:207-216.