Research Interests

We list here some of the major active projects ongoing in our laboratories, along with some of the people in our groups working on the projects. Click on each project to learn more, including publications and a brief description.

Some of our group's recent publications are listed below.


Neuron-Astrocyte Interactions

Astrocytes support a functional nervous system, but their full role remains incompletely understood.
First described as structural cells with the sole responsibility of supporting neuronal physiology, astrocytes are
now credited as active players in areas such as synaptic function, neuronal metabolism, and extracellular ion
homeostasis. Despite our increased understanding of the relationship between neurons and astrocytes, technical hurdles still impede much of our knowledge. The inability to remove astrocytes from a neuronal circuit without changing many additional variables profoundly inhibits our ability to explore the astrocyte-neuron relationship completely.

We have developed a novel system that explores the consequence of removing local astrocytic support from neurons while leaving all other conditions intact. We grow solitary neurons in microcultures that either contain astrocyte beds (+astrocyte neurons) or lack astrocyte beds (-astrocyte neurons), under otherwise identical conditions.

We have found that -astrocyte neurons have severely disrupted glutamate release synchrony, but GABA release is unaffected. This appears to be due to aberrant action potential propagation along the axon of neurons grown without local astrocyte support. We are currently interested in further elucidating the mechanism surrounding this phenomenon as well as exploring the roles of astrocytes in other neuronal functions.



We are collaborating with Doug Covey’s lab in the Department of Molecular Biology & Pharmacology and with Joe Henry Steinbach, Gustav Akk, and Alex Evers in the Anesthesiology Department to understand regulation of GABA and glutamate receptors by neurosteroids. Neurosteroids are synthesized within the CNS and have direct actions on ligand-gated ion channels, notably GABA-A receptor and NMDA receptors. We have been particularly interested in GABA receptor modulation because these receptors are likely modulated by endogenous levels of neurosteroids.

Recent work has focused on understanding the importance of membrane partitioning in the access of neurosteroids to the GABA-A receptor. For this work we have used fluorescently tagged neurosteroid analogs to follow steroid movement into and out of neurons. An unexpected recent finding was that these tagged steroids are sometimes inert until excited with appropriate wavelengths of light, at which time they become active at GABA receptors. Other recent work has focused on understanding other novel neuromodulators, particularly those acting at NMDA-type glutamate receptors.

Recent work with neurosteroids and other modulators have recently led to the establishment of the Taylor Family Institute for Innovative Psychiatric Research, centered on discovery of novel pharmacological strategies for treating psychiatric disease.


Fast biosensors of dopamine release

“Slow” transmitters like dopamine are critically important to reward, attention, and neuropsychiatric disease. However, unlike fast neurotransmitters (e.g., glutamate), whose ligand-gated ion channels give us a faithful, linear readout of release of the cognate neurotransmitter, dopamine GPCRs do not give a faithful readout of the timing, plasticity, and modulation of dopamine release. Presynaptic imaging and electrochemistry are partial but ultimately unsatisfying solutions to the issue. We have set about making fast dopamine synapses by heterologously introducing a ligand-gated dopamine receptor with properties that make it a good synaptic biosensor for dopamine. With this approach we hope to study the modulation of dopamine release with resolution not heretofore possible.



Budding collaborations with other WU investigators include study of GPCR regulation, the study of tonic vs. phasic GABA signaling, and the study of the physiological properties of neurons re-programmed from patient skin samples. We are also collaborating with Dr. Larry Eisenman (WU Neurology) to develop tools for analysis of connectivity in small neural networks. Other collaborations include studies with Dr. Bruce Carlson to study sensory processing in weakly electric fish using single-axon recording techniques, and Dr. Andrew Yoo to characterize excitability of newly converted neurons from human fibroblasts.

Recent Publications
  1. Loss of local astrocyte support disrupts action potential propagation and glutamate release synchrony from unmyelinated hippocampal axon terminals in vitro

    Sobieski C, Jiang X, Crawford DC, Mennerick S.

    J Neurosci. 2015 Aug 5

  2. Fast phasic release properties of dopamine studied with a channel biosensor.

    Kress GJ, Shu HJ, Yu A, Taylor A, Benz A, Harmon S, Mennerick S.

    J Neurosci. 2014 Aug 27

  3. Acute and chronic effects of ethanol on learning-related synaptic plasticity.

    Zorumski CF, Mennerick S, Izumi Y.

    Alcohol. 2014 Feb.

  4. Indistinguishable synaptic pharmacodynamics of the N-methyl-D-aspartate receptor channel blockers memantine and ketamine.

    Emnett CM, Eisenman LN, Taylor AM, Izumi Y, Zorumski CF, Mennerick S.

    Mol Pharmacol. 2013

  5. Non-competitive, Voltage-dependent NMDA Receptor Antagonism by Hydrophobic Anions.

    Linsenbardt A, Chisari M, Yu A, Shu HJ, Zorumski CF,Mennerick SJ.

    Mol Pharmacol. 2012 Nov 9.

  6. Astrocyte-derived thrombospondins mediate the development of hippocampal presynaptic plasticity in vitro.

    Crawford DC, Jiang X, Taylor A, Mennerick S.

    J Neurosci.2012 Sep 19;32(38):13100-10.

  7. Synaptic NMDA receptors mediate hypoxic excitotoxic death.

    Wroge CM, Hogins J, Eisenman L, Mennerick S.

    J Neurosci. 2012 May 9;32(19):6732-42.

  8. Cross talk between synaptic receptors mediates NMDA-induced suppression of inhibition.

    Chisari M, Zorumski CF, Mennerick S.

    J Neurophysiol. 2012 May;107(9):2532-40.

  9. Excitotoxicity triggered by Neurobasal culture medium.

    Hogins J, Crawford DC, Zorumski CF, Mennerick S.

    PLoS One. 2011;6(9):e25633.

  10. Characteristics of concatemeric GABA(A) receptors containing α4/δ subunits expressed in Xenopus oocytes.

    Shu HJ, Bracamontes J, Taylor A, Wu K, Eaton MM, Akk G, Manion B, Evers AS, Krishnan K, Covey DF, Zorumski CF, Steinbach JH, Mennerick S.

    Br J Pharmacol. 2012 Apr;165(7):2228-43. 

  11. Presynaptically silent synapses: dormancy and awakening of presynaptic vesicle release.

    Crawford DC, Mennerick S.

    Neuroscientist. 2012 Jun;18(3):216-23. 

  12. Presynaptic silencing is an endogenous neuroprotectant during excitotoxic insults.

    Hogins J, Crawford DC, Jiang X, Mennerick S.

    Neurobiol Dis. 2011 Aug;43(2):516-25.

  13. Hydrophobic anions potently and uncompetitively antagonize GABA(A) receptor function in the absence of a conventional binding site.

    Chisari M, Wu K, Zorumski CF, Mennerick S.

    Br J Pharmacol. 2011 Sep;164(2b):667-80.

  14. Calcium-independent inhibitory G-protein signaling induces persistent presynaptic muting of hippocampal synapses.

    Crawford DC, Chang CY, Hyrc KL, Mennerick S.

    J Neurosci. 2011 Jan 19;31(3):979-91.