Mark P. Beenhakker
Circuit mechanisms of sleep and epilepsy
Our lab aims to understand how the brain generates complex electrical signals, and how these signals are used to process information. A major extension of this aim is to understand why electrical activity in the brain becomes uncontrollable during certain diseases such as epilepsy. We use electrophysiological, anatomical and computational approaches to resolve these questions.
We primarily focus on cellular- and circuit-level questions in the thalamus, a structure that is generally believed to function as a relay station between the outside world and the cortex. However, the thalamus also plays a critical role in generating rhythmic network activity that is thought to facilitate the consolidation of memories during sleep. Furthermore, seizures associated with some forms of childhood/juvenile epilepsy are thought to be driven by thalamic circuits. Thus, the thalamus is engaged in several different processes, both normal and pathological. Designing experiments to resolve the mechanisms that underlie these processes forms the core of our research.
Current projects in the lab focus on the:
- excessive excitability of thalamic neurons associated with chloride channel dysfunction.
- network-level activity patterns observed in the thalamus during sleep and epilepsy.
- regulation of metabotropic signaling carried out by thalamic neurons.
- Lee A, Wang G, Jiang X, Johnson S, Hoang E, Lanté F, Stornetta R, Beenhakker M, Shen Y, Julius Zhu J. Canonical Organization of Layer 1 Neuron-Led Cortical Inhibitory and Disinhibitory Interneuronal Circuits. Cerebral cortex (New York, N.Y. : 1991). 2014. PMID: 24554728
- Beenhakker M, Huguenard J. Astrocytes as gatekeepers of GABAB receptor function. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2010;30(45): 15262-76. PMID: 21068331 | PMCID: PMC3056552
- Beenhakker M, Huguenard J. Neurons that fire together also conspire together: is normal sleep circuitry hijacked to generate epilepsy? Neuron. 2009;62(5): 612-32. PMID: 19524522 | PMCID: PMC2748990
- Bryant A, Li B, Beenhakker M, Huguenard J. Maintenance of thalamic epileptiform activity depends on the astrocytic glutamate-glutamine cycle. Journal of neurophysiology. 2009;102(5): 2880-8. PMID: 19741104 | PMCID: PMC2777838
- DeLong N, Beenhakker M, Nusbaum M. Presynaptic inhibition selectively weakens peptidergic cotransmission in a small motor system. Journal of neurophysiology. 2009;102(6): 3492-504. PMID: 19828722 | PMCID: PMC2804423
- Kleiman-Weiner M, Beenhakker M, Segal W, Huguenard J. Synergistic roles of GABAA receptors and SK channels in regulating thalamocortical oscillations. Journal of neurophysiology. 2009;102(1): 203-13. PMID: 19386752 | PMCID: PMC2712277
- Beenhakker M, Kirby M, Nusbaum M. Mechanosensory gating of proprioceptor input to modulatory projection neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27(52): 14308-16. PMID: 18160638
- Beenhakker M, DeLong N, Saideman S, Nadim F, Nusbaum M. Proprioceptor regulation of motor circuit activity by presynaptic inhibition of a modulatory projection neuron. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005;25(38): 8794-806. PMID: 16177049
- Beenhakker M, Nusbaum M. Mechanosensory activation of a motor circuit by coactivation of two projection neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004;24(30): 6741-50. PMID: 15282277
- Christie A, Stein W, Quinlan J, Beenhakker M, Marder E, Nusbaum M. Actions of a histaminergic/peptidergic projection neuron on rhythmic motor patterns in the stomatogastric nervous system of the crab Cancer borealis. The Journal of comparative neurology. 2003;469(2): 153-69. PMID: 14694531
- Nusbaum M, Beenhakker M. A small-systems approach to motor pattern generation. Nature. 2002;417(6886): 343-50. PMID: 12015615