Howard, Mackenzie

Mackenzie A Howard

Research Assistant Professor (Affiliated), Research Assistant Professor
Department of Neuroscience


Discovering cellular and circuit mechanisms of cognitive dysfunction in epilepsy and neurodevelopmental disorders

mackenziehoward@austin.utexas.edu


Office Location
NHB 2.124

Postal Address
The University of Texas at Austin
Department of Neuroscience, College of Natural Sciences
1 University Station C7000
Austin, TX 78712

I received my BA in Biology from Lewis and Clark College in Portland, Oregon, in 1998. During and after my undergraduate years I narrowed my focus to neuroscience while working on research projects in labs at Oregon Health Sciences University, University of Miami, and University of Colorado Health Sciences Center. I then joined Ed Rubel’s lab in the Department of Physiology and Biophysics at the University of Washington. I completed my dissertation studying how the development and integration of excitatory and inhibitory inputs with intrinsic neuronal properties allows for neural processing of auditory information, and received my PhD in 2008. I completed two postdoctoral fellowships at UCSF, shifting my focus to the cellular and circuit mechanisms of synaptic plasticity and connectivity in epilepsy and neurodevelopmental disease. I joined the UT faculty in 2017.

The overall goal of my research is to discover the causative cellular and neural circuit changes linking neurological disease mutations with cognitive deficits. Genetic epilepsies give rise to seizures, and often additionally cause wide-ranging and severe cognitive deficits to sensory integration, movement control, learning and memory, sleep, and mood regulation. I use genetic mouse models of epilepsy to define the roles of specific neuron subtypes in information processing by cortical microcircuits. I am specifically interested in the mechanisms by which monogenic disease mutations initially alter the physiological properties of individual cell subtypes, and the subsequent cascading effects on activity, synaptic connectivity and plasticity, and circuit function. I use molecular genetic manipulations with a variety in vitro and in vivo electrophysiological, imaging, and behavioral techniques to study neural activity at the level of single cells, cell subtypes, and circuits.

Howard MA, Baraban SC (2017, in press). Catastrophic epilepsies of childhood.  Annual Review of Neuroscience.

Pla R, Stanco A, Howard MA, Vogt D, Rubin A, Mortimer N, Cobos I, Potter GP, Lindtner S, Scott C. Baraban, Rowitch DH, Rubenstein JLR (in revision, Nature Communications). Dlx1/2 are involved in cortical interneurons maturation promoting synaptogenesis, GABA synthesis and dendrite outgrowth through Grin2b.

Howard MA, Baraban SC (2016). Synaptic integration of transplanted interneuron progenitor cells into native cortical networks. Journal of Neurophysiology, 116, 472-8.

Silbereis JC, Nobuta H, Tsai H-H, Heine VM, McKinsey GL, Meijer DH, Petryniak MA, Potter GP, Howard MA, Alberta JA, Baraban SC, Stiles CD, Rubenstein JLR, Rowitch DH (2014). Olig1 function is required to repress Dlx1/2 and interneuron production in mammalian brain. Neuron, 81, 574-87.

Howard MA, Rubenstein JLR, Baraban SC (2014). Bidirectional homeostatic plasticity induced by interneuron cell death and transplantation in vivo. Proceedings of the National Academy of Science, USA, 111, 492-7.

Russell JF, Steckley JL, Coppola G, Hahn AF, Howard MA, Kornberg Z, Huang A, Mirsattari SM, Merriman B, Klein E, Choi M, Lee HY, Kirk A, Nelson-Williams C, Gibson G, Baraban SC, Lifton RP, Geschwind DH, Fu YH, Ptáček LJ (2012). Familial cortical myoclonus with a mutation in NOL3. Annals of Neurology, 72, 175-83.

Jones DL, Howard MA, Stanco A, Rubenstein JL, Baraban SC (2011). Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons. Journal of Neurophysiology, 105, 1984-91.

Howard MA, Elias GM, Elias LA, Swat W, Nicoll RA (2010).  The role of SAP97 in synaptic glutamate receptor dynamics. Proceedings of the National Academy of Science, USA, 107, 3805-10.

Howard MA, Rubel EW (2010). Dynamic spike thresholds during synaptic integration preserve and enhance temporal response properties in the avian cochlear nucleus. Journal of Neuroscience, 30, 12063-74.

Howard MA, Burger RM, Rubel EW (2007).  A developmental switch to GABAergic inhibition dependent on increases in Kv1-type K+ currents.  Journal of Neuroscience, 27, 2112-23.

Martin GL, Vazquez AE, Jimenez AM, Stagner BB, Howard MA, Lonsbury-Martin BL (2007).  Comparison of distortion product otoacoustic emissions in 28 inbred strains of mice.  Hearing Research, 234, 59-72. 

Howard MA, Stagner BB, Lonsbury-Martin BL, Martin GK (2003).  Suppression tuning in noise exposed rabbits.  Journal of the Acoustical Society of America, 114, 279-93.

Howard MA, Rodenas-Ruana AI, Henkemeyer M, Martin GK, Lonsbury-Martin BL, Liebl DJ (2003).  Eph receptor deficiencies lead to altered cochlear function.  Hearing Research, 178, 118-30.

Cunningham CL, Ferree NK, Howard MA (2003).  Initial cue bias and place conditioning. Psychopharmacology, 170, 409-22.

Kinoshita K, Chatzipanteli K, Alonso OF, Howard MA, Dietrich WD (2002).  The effect of brain temperature on hemoglobin extravasation after traumatic brain injury.  Journal of Neurosurgery, 97, 945-953.

Howard MA, Stagner BB, Lonsbury-Martin BL, Martin GK (2002).  Effects of reversible noise exposure on the suppression tuning of rabbit distortion-product otoacoustic emissions.  Journal of the Acoustical Society of America, 111, 285-96.

Cunningham CL, Howard MA, Gill SJ, Rubinstein M, Low MJ, Grandy DK (2000). Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice.  Pharmacology, Biochemistry and Behavior, 67, 693-9.