Matthew J.M. Rowan
Emory University, GA·Neuroscience
Studying one kind of neuron at a time requires a way to reach only that cell type, in order to label it, record from it, or turn it on and off. Two projects build that kind of targeted access and then apply it to the hippocampus, a brain structure central to memory and spatial navigation, and to the early circuit changes seen in Alzheimer's disease.
- Fields
Neuroscience
Biomedical Engineering
Biology
- Topics
hippocampus
Alzheimer's disease
parvalbumin interneurons
- Grants
- 2 known grants, through Mar 2028
What they work on
- Develop enhancer-AAVs, viruses carrying cell-type-selective DNA switches, that label dentate gyrus granule cells, and convert the best candidates into optogenetic and chemogenetic variants for controlling these neurons.
- Extend selective viral targeting to other hippocampal excitatory neurons, including CA1, CA2 and CA3 pyramidal cells and hilar mossy cells, screening candidate enhancers chosen from public hippocampal RNA sequencing data.
- Test whether parvalbumin-expressing inhibitory interneurons develop firing and neurotransmission deficits first in the brain regions most vulnerable to Alzheimer's disease, then in other areas.
- Record thousands of fluorescently labeled interneurons using the PatcherBot, a robot that performs automated patch-clamp recordings in brain slices, upgraded with fluorescence imaging for cell-type-specific targeting.
- Compare circuit changes across entorhinal cortex, hippocampus and isocortex in APOE4, humanized APP knock-in and 5xFAD mice at three ages to chart how dysfunction spreads.
More about the research
One project develops viral tools for precise genetic access to hippocampal cell types. The hippocampus is heavily studied, but researchers have lacked reliable ways to target its individual subfields, which limits techniques like optogenetics (controlling neurons with light) and chemogenetics (controlling them with designer drugs). The approach uses enhancer-AAVs: adeno-associated virus vectors carrying short DNA regulatory sequences that switch a gene on only in one neuron type. Candidate enhancers are picked from a public hippocampal RNA sequencing dataset, which reports which genes each cell type expresses. Preliminary results show highly specific labeling of dentate gyrus granule cells, the hippocampus's input neurons, and the lab will build optogenetic and chemogenetic versions of those viruses. Work then extends to CA3, CA2 and CA1 pyramidal cells and hilar mossy cells, with the goal of distributing tools the wider community can use.
Why it matters
Dementia is projected to affect over 150 million people by 2050, with Alzheimer's disease the majority of cases, and treatments that halt early disease remain elusive. Mapping when and where inhibitory neurons first falter could identify cells and time windows to target before degeneration sets in. The hippocampus-specific viral tools could also serve researchers studying memory, epilepsy and Alzheimer's, and may form the basis of future gene-delivery therapies.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Stefano Fusi
Columbia University, NY·Neuroscience
Test whether adult-born granule cells in the dentate gyrus support sparse memory encoding that enables pattern separation, combining neural recordings in mice with computational modeling.
Alison Barth
Carnegie Mellon University, PA·Neuroscience
Map the circuit connections of a molecularly defined subtype of somatostatin (SST) inhibitory neurons in superficial mouse sensory cortex, and how they change during whisker-reward learning, using cell-type- and pathway-specific brain slice recordings.
Barna Dudok
Baylor College of Medicine, TX·Neuroscience·Early-career
Test whether CCK and PV basket cells, two types of inhibitory neurons, are active in different brain states in a kainate mouse model of temporal lobe epilepsy, using two-photon calcium imaging with hippocampal field recordings.
The school
Emory University: 70 labs on PI Pages, $1.2B a year on research, 286 research doctorates a year.
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