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Allan Gulledge, PhD

Title(s)
Professor of Molecular and Systems Biology

Department(s)
Molecular and Systems Biology

Education
University of California, Riverside, BS 1991
University of Texas, San Antonio, PhD 2000

Programs
Neuroscience Center at Dartmouth
Program in Experimental and Molecular Medicine

Websites
https://geiselmed.dartmouth.edu/gulledge/
https://geiselmed.dartmouth.edu/msb/
https://sites.dartmouth.edu/ind/

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Contact Information

Geisel School of Medicine
74 College Street
Vail 601
Hanover NH 03755

Office: Vail 601
Phone: 603-646-5249
Email: allan@dartmouth.edu

Asst. Phone: 603-646-5250


Professional Interests

Our research focus is the cerebral cortex, an area of the brain that serves as the biological substrate for the higher cognitive functions that define us as individuals. We wish to identify the mechanisms by which individual cortical neurons process and transmit information within the cortical circuit. To accomplish this we employ electrical and optical recording techniques that measure neuronal activity in neocortical neurons under a variety of experimental conditions.

Currently, we are investigating signal transduction events that are mediated by a variety of "modulatory" neurotransmitters that are critical for normal cognition and directly involved in many neurological and psychiatric disorders. These modulators (such as acetylcholine, serotonin, and dopamine) activate a variety of receptor subtypes to initiate biochemical signaling cascades within neurons that influence excitability and synaptic transmission. Because there are many different cell types within the cortex, each expressing a unique combination of receptors, neuromodulators can have different, or even opposite, effects on specific neuronal subpopulations. By examining how neuromodulators regulate the activity of many types of cortical neuron, we aim to identify their functional role in facilitating information flow within cortical circuits. This knowledge will provide insight into normal cognition, and may reveal mechanisms contributing to neurological and psychiatric disorders, such as major depression, schizophrenia, and age-dependent dementia.

Rotations and Thesis Projects

There are a great many mysteries regarding the physiology of the neocortex that remain to be discovered. Among other opportunities, students may wish to consider:

1. Identification of the molecular mechanism(s) by which G-protein-coupled receptors regulate the output of cortical neurons.
2. Characterization of the synaptic release processes that are modified by presynaptic metabotropic and ionotropic receptors.
3. Determination of the role of calcium in regulating the activity of cortical neurons.
4. Revealing plasticity in serotonin receptor expression in cortical neurons driven by selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine.
5. Characterizing the impact of neuronal morphology in synaptic integration.

More information available at https://geiselmed.dartmouth.edu/gulledge/

Grant Information

R01 MH124934: Coordinated modulation of cortical circuits by serotonin and acetylcholine
Project period: 09/13/21-06/30/26
PI: Allan Gulledge

R01 MH099054: Neuromodulation of cortical circuits in health and disease
Project period: 08/01/13-07/31/18
PI: Allan Gulledge

R01-MH083806: Cholinergic signaling in cortical neurons: a unifying hypothesis
Project period: 07/11/08-06/30/13
PI: Allan Gulledge

NSF 0922631: MRI: Acquisition of a multi-photon imaging and electrophysiology rig
Project period: 08/01/2009 - 07/31/2012
PI: Allan Gulledge

NARSAD Young Investigator Award (2009): CCK-Positive Large Basket Neurons as a Source of Cortical Activation in ADHD
Project Period: 01/01/2010 - 12/31/2012
PI: Allan Gulledge

Neuroscience Center at Dartmouth Collaborative/Translational Funding Award: Cholinergic mechanisms involved in cue discrimination
Project Period: 01/01/2008 - 01/01/2009
PI: Allan Gulledge & David Bucci

Courses Taught

IND 103: Advanced Techniques in Neuroscience (2022 - Present)
IND 700: Responsible and Ethical Conduct of Research (2022 - Present)
IND 600: Neuroscience Journal Club (2022 - 2023)
PEMM 700: Responsible and Ethical Conduct of Research (2020, 2021)
IND 115: Foundational Neuroscience (2020, 2021)
IND 124: Ethical Conduct in Research (2022 - Present)
RECR Facilitators training course (2018 - Present)
PEMM 131: Experimental Therapeutics (2018)
PEMM 124: Responsible and Ethical Conduct of Research (2012 - 2021)
PEMM 212: Neurosciences II (2014, 2016, 2018)
PEMM Neuroscience Journal Club (2014, 2015, 2016)
PEMM 211: Neurobiology of disease (2010, 2011, 2014)
PEMM 271: Advanced Biomedical Sci (2008, 2010, 2012)
UNSG 100: Responsible and Ethical Conduct of Research (2009 - 2018)
PEMM 101: Scientific basis of disease (2009 - 2019)
PHSL 110: Cardiovascular Physiology (2009 - 2015)
MDED 115: Medical Neuroscience (2008 - 2019)

Mentoring Information

Sameera Dasari, PhD (2009-2012)
Daniel Avesar, PhD (2008-2013)
Emily Stephens, PhD (2012-2017)
Arielle Baker, PhD (2015-2019)
Chenguang Li, B.S. (2015-2018)
Keita Onoue, M.D. (2011)

Primary mentor to 22 Dartmouth Undergraduates
Dissertation committee member for 12 graduate students

Postdoc mentoring award (2011)
Graduate student mentoring award (2016)

Biography

Dr. Gulledge received his B.S. in Psychobiology from the University of California, Riverside in 1991, and his Ph.D. in Biology from the University of Texas, San Antonio in 2000. He then conducted postdoctoral research at the Australian National University (2000-2005) as an NSF International Research Fellow, and at the National Institute for Physiological Sciences in Okazaki, Japan (2005-2007), as a JSPS Postdoctoral Fellow. Dr. Gulledge joined the faculty of Dartmouth Medical School as an Assistant Professor of Physiology in 2007, and is now a Professor of Molecular and Systems Biology.


Selected Publications

 

Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics.
DeSpenza T Jr, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina ML, Desmet N, Dang HQ, Fields J, Nelson-Williams C, Zhang J, Mekbib KY, Dennis E, Mehta NH, Duy PQ, Shimelis H, Walsh LK, Marlier A, Deniz E, Lake EMR, Constable RT, Hoffman EJ, Lifton RP, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper SL, Jin SC, Kahle KT, Luikart BW
Proc Natl Acad Sci U S A. 2024 Jul 2;121(27):e2314702121. doi: 10.1073/pnas.2314702121. Epub 2024 Jun 25.
PMID: 38916997

Cholinergic Activation of Corticofugal Circuits in the Adult Mouse Prefrontal Cortex.
Gulledge AT
J Neurosci. 2024 Jan 17;44(3) doi: 10.1523/JNEUROSCI.1388-23.2023. Epub 2024 Jan 17.
PMID: 38050146

Cholinergic activation of corticofugal circuits in the adult mouse prefrontal cortex.
Gulledge AT
bioRxiv. 2023 Jul 22; pii: 2023.04.28.538437. doi: 10.1101/2023.04.28.538437. Epub 2023 Jul 22.
PMID: 37163128

Postrhinal cortex contributions to the expression of auditory fear conditioning.
DeAngeli NE, Fournier DI, Gulledge AT, Burwell RD, Todd TP, Bucci DJ
Neurobiol Learn Mem. 2022 May;191:107609. doi: 10.1016/j.nlm.2022.107609. Epub 2022 Mar 8.
PMID: 35276336

Retrosplenial cortex inactivation during retrieval, but not encoding, impairs remotely acquired auditory fear conditioning in male rats.
Fournier DI, Cheng HY, Tavakkoli A, Gulledge AT, Bucci DJ, Todd TP
Neurobiol Learn Mem. 2021 Nov;185:107517. doi: 10.1016/j.nlm.2021.107517. Epub 2021 Sep 6.
PMID: 34500052

Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type.
Contreras SA, Schleimer JH, Gulledge AT, Schreiber S
PLoS Comput Biol. 2021 May;17(5):e1008510. doi: 10.1371/journal.pcbi.1008510. Epub 2021 May 27.
PMID: 34043638

NMDA Receptors Enhance the Fidelity of Synaptic Integration.
Li C, Gulledge AT
eNeuro. 2021 Mar-Apr;8(2) pii: ENEURO.0396-20.2020. doi: 10.1523/ENEURO.0396-20.2020. Epub 2021 Mar 3.
PMID: 33468538

Corrigendum: Mechanisms Underlying Serotonergic Excitation of Callosal Projection Neurons in the Mouse Medial Prefrontal Cortex.
Stephens EK, Baker AL, Gulledge AT
Front Neural Circuits. 2019;13:23. doi: 10.3389/fncir.2019.00023. Epub 2019 Apr 9.
PMID: 31024266

Loss of Neurofascin-186 Disrupts Alignment of AnkyrinG Relative to Its Binding Partners in the Axon Initial Segment.
Alpizar SA, Baker AL, Gulledge AT, Hoppa MB
Front Cell Neurosci. 2019;13:1. doi: 10.3389/fncel.2019.00001. Epub 2019 Jan 22.
PMID: 30723396

Serotonergic Regulation of Corticoamygdalar Neurons in the Mouse Prelimbic Cortex.
Avesar D, Stephens EK, Gulledge AT
Front Neural Circuits. 2018;12:63. doi: 10.3389/fncir.2018.00063. Epub 2018 Aug 7.
PMID: 30131678

View more publications on PubMed