A theme of our research is to establish a mechanistic link between pathological changes in synaptic and dendritic function, with an emphasis on voltage-gated ion channels, and behavioral phenotypes in neurological diseases and disorders. We employ a broad array of techniques including the preparation of acute brain slices, elcectrophysiological recording including direct dendritic recording, patch clamp recording, electrical and optogenetic synaptic stimulation and two-photon calcium imaging. We supplement these approaches with immunohistochemistry, western blotting, and neuronal reconstruction .

Ordemann, G. J., Apgar, C. J. & Brager, D. H. D-type potassium channels normalize action potential firing between dorsal and ventral CA1 neurons of the mouse hippocampus. J Neurophysiol 121, 983–995 (2019).

Routh, B. N. et al.Increased transient Na +conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1 −/ymouse. J Physiol (Lond) 595, 4431–4448 (2017).

Kim, C. S., Brager, D. H. & Johnston, D. Perisomatic changes in h-channels regulate depressive behaviors following chronic unpredictable stress. Mol. Psychiatry(2017). doi:10.1038/mp.2017.28

Kalmbach, B. E., Johnston, D. & Brager, D. H. Cell-Type Specific Channelopathies in the Prefrontal Cortex of the fmr1-/y Mouse Model of Fragile X Syndrome. eNeuro 2,(2015).

Sosanya, N. M., Brager, D. H., Wolfe, S., Niere, F. & Raab-Graham, K. F. Rapamycin reveals an mTOR-independent repression of Kv1.1 expression during epileptogenesis. Neurobiol Dis 73, 96–105 (2015).

Brager, D. H. & Johnston, D. Channelopathies and dendritic dysfunction in fragile X syndrome. Brain Res Bull 103, 11–17 (2014).

Routh, B. N., Johnston, D. & Brager, D. H. Loss of Functional A-Type Potassium Channels in the Dendrites of CA1 Pyramidal Neurons from a Mouse Model of Fragile X Syndrome. Journal of Neuroscience 33, 19442–19450 (2013).

Brager, D. H., Lewis, A. S., Chetkovich, D. M. & Johnston, D. Short- and long-term potentiation in CA1 neurons from mice lacking the h-channel auxiliary subunit TRIP8b. J Neurophysiol(2013). doi:10.1152/jn.00218.2013

Brager, D. H., Akhavan, A. R. & Johnston, D. Impaired dendritic expression and plasticity of h-channels in the fmr1(-/y) mouse model of fragile X syndrome. Cell Reports 1, 225–233 (2012).

Lewis, A. S. et al.Deletion of the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Auxiliary Subunit TRIP8b Impairs Hippocampal Ih Localization and Function and Promotes Antidepressant Behavior in Mice. J Neurosci 31, 7424–7440 (2011).

Shin, M., Brager, D., Jaramillo, T. C., Johnston, D. & Chetkovich, D. M. Mislocalization of h channel subunits underlies h channelopathy in temporal lobe epilepsy. Neurobiol Dis 32, 26–36 (2008).

Brager, D. H. & Johnston, D. Plasticity of intrinsic excitability during long-term depression is mediated through mGluR-dependent changes in I(h) in hippocampal CA1 pyramidal neurons. J Neurosci 27, 13926–13937 (2007).

Fan, Y. et al.Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h). Nat Neurosci 8, 1542–1551 (2005).

Heinbockel, T. et al.Endocannabinoid signaling dynamics probed with optical tools. J Neurosci 25, 9449–9459 (2005).

Brager, D. H., Luther, P. W., Erdélyi, F., Szabó, G. & Alger, B. E. Regulation of exocytosis from single visualized GABAergic boutons in hippocampal slices. J Neurosci 23,10475–10486 (2003).

Brager, D. H., Cai, X. & Thompson, S. M. Activity-dependent activation of presynaptic protein kinase C mediates post-tetanic potentiation. Nat Neurosci 6, 551–552 (2003).

Brager, D. H. & Thompson, S. M. Activity-dependent release of adenosine contributes to short-term depression at CA3-CA1 synapses in rat hippocampus. J Neurophysiol 89, 22–26 (2003).

Varma, N. et al.Presynaptic factors in the regulation of DSI expression in hippocampus. Neuropharmacology 43, 550–562 (2002).

Brager, D. H., Capogna, M. & Thompson, S. M. Short-term synaptic plasticity, simulation of nerve terminal dynamics, and the effects of protein kinase C activation in rat hippocampus. J Physiol (Lond) 541, 545–559 (2002).

Brager, D. H., Sickel, M. J. & McCarthy, M. M. Developmental sex differences in calbindin-D(28K) and calretinin immunoreactivity in the neonatal rat hypothalamus. 42, 315–322 (2000).

Greg Ordemann, INS graduate student

Lauren Hewitt, INS graduate student