Research

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Todd E. Anthony, PhD

Todd Anthony PhD
Research Center:
F.M. Kirby Neurobiology Center
Program:
Neurobiology Program
Department:
PsychiatryNeurology Research
Hospital Title:
Research Associate
Academic Title:
Assistant Professor, Harvard Medical School
Research Focus Area:
Genetic dissection of neural circuits that control stress-induced behavioral states
Contact:
617-919-2200

Research Overview

Even a single traumatic experience can trigger the onset of a negatively valenced affective state that persists for days to weeks. Adaptive properties of such states include hyperarousal and heightened vigilance, but their excessive duration and/or severity can lead to pathological conditions such as post-traumatic stress disorder (PTSD) and severe depression. What are the neural and molecular substrates responsible for the induction, persistence and severity of such states? Why do even genetically identical individuals show differential susceptibility to mood disorders precipitated by stress? Can specific pharmacological or genetic manipulations be developed in the lab that can prevent or reverse stress-induced psychiatric disorders in people?

We are addressing these questions by focusing on the lateral septal (LS) node of the septohippocampal system, a pathway long implicated in the control of stress-induced behavioral states but which has received relatively little attention in the modern era. Although often overlooked, the LS is likely to play critical roles in human affective disorders as it is robustly activated by stressful stimuli and required for persistent behavioral responses to stress (e.g. increased anxiety). However, the LS is a large, highly heterogeneous structure containing tens if not hundreds of distinct cell types that also mediate other, apparently disparate behavioral functions (e.g. social behavior, drug abuse, sexual pleasure). Which specific neuronal or glial populations subserve which functions via which pathways remains virtually unknown.

To target defined components of LS stress circuitry, we are taking a genetic approach that combines mouse molecular genetics, viral vectors, behavioral analysis, calcium imaging, and electrophysiological approaches to causally link the activity of specific circuits and/or genes to the persistent behavioral effects of stress. In addition to ‘gene-based’ targeting of cell types, we are also developing and employing novel activity-dependent genetic tools to interrogate neuronal subpopulations activated in response to different stress paradigms.

About Todd Anthony

Dr. Anthony received his PhD at the Rockefeller University in the laboratory of Nathaniel Heintz, and did his postdoctoral work at the California Institute of Technology with David Anderson. He was the recipient of a Ruth Kirchstein NIH NRSA postdoctoral fellowship for behavioral neuroscience, and awarded a Beckman Institute Fellowship to fund his work on development of novel molecular genetic approaches for activity-dependent neural circuit manipulation.

Publications

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  1. Kim E, Wang Y, Kim SJ, Bornhorst M, Jecrois ES, Anthony TE, Wang C, Li YE, Guan JL, Murphy GG, Zhu Y. Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1. Elife. 2014 Dec 23; 3.
  2. Cai H, Haubensak W, Anthony TE, Anderson DJ. Central amygdala PKC-d(+) neurons mediate the influence of multiple anorexigenic signals. Nat Neurosci. 2014 Sep; 17(9):1240-8.
  3. Anthony TE, Dee N, Bernard A, Lerchner W, Heintz N, Anderson DJ. Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit. Cell. 2014 Jan 30; 156(3):522-36.
  4. Anthony TE, Heintz N. Cre-ating somatic cell genetic mosaics in the mouse. Cell. 2005 May 6; 121(3):322-3.
  5. Anthony TE, Azmitia EC. Molecular characterization of antipeptide antibodies against the 5-HT1A receptor: evidence for state-dependent antibody binding. Brain Res Mol Brain Res. 1997 Oct 15; 50(1-2):277-84.
  6. Anthony TE, Heintz N. The folate metabolic enzyme ALDH1L1 is restricted to the midline of the early CNS, suggesting a role in human neural tube defects. J Comp Neurol. 2007 Jan 10; 500(2):368-83.
  7. Anthony TE, Mason HA, Gridley T, Fishell G, Heintz N. Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells. Genes Dev. 2005 May 1; 19(9):1028-33.
  8. Anthony TE, Klein C, Fishell G, Heintz N. Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron. 2004 Mar 25; 41(6):881-90.
  9. Anthony TE, Heintz N. Genetic lineage tracing defines distinct neurogenic and gliogenic stages of ventral telencephalic radial glial development. Neural Dev. 2008 Nov 05; 3:30.
  10. Lee H, Kim DW, Remedios R, Anthony TE, Chang A, Madisen L, Zeng H, Anderson DJ. Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus. Nature. 2014 May 29; 509(7502):627-32.
  11. Show all
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RELATED RESEARCH CENTER

F.M. Kirby Neurobiology Center

The F.M. Kirby Neurobiology Center, together with the Neurobiology Program at Boston Children’s Hospital, is the largest basic neuroscience research enterprise at a U.S. hospital. It incorporates basic and translational neuroscience research, focusing primarily on developmental neurobiology.

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