About

Douglas A. Coulter, PhD, is an Emeritus Professor of Pediatrics (Neurology) in the Department of Pediatrics at the Perelman School of Medicine, University of Pennsylvania. His research interests center on understanding the cellular and molecular mechanisms underlying the development of epilepsy, with a focus on symptomatic seizure disorders such as temporal lobe epilepsy. His laboratory employs physiological, functional imaging, anatomical, and molecular techniques to investigate epilepsy, utilizing methods such as patch clamp recordings, calcium imaging, microscopy, immunohistochemistry, and EEG recordings in both in vitro and in vivo preparations of animal and human brain. Dr. Coulter's work aims to elucidate seizure-initiating mechanisms to facilitate the development of improved therapeutic strategies and potentially contribute to a cure for epilepsy. His research explores neuronal excitability, CNS rhythm generation, circuit imaging, GABA receptors, and the development of neurotransmitter receptors and ion channels. His contributions include advancing understanding of the cellular and circuit alterations in epileptic brains, with a particular emphasis on hippocampal and neocortical changes, and the molecular pathways involved in seizure activity.

Research topics

• Physics
• Astrophysics
• Astronomy

Selected publications

• Reducing ventral hippocampal CA1/subiculum hyperexcitability restores social memory and alleviates anxiety-related behavior in a mouse model of temporal lobe epilepsy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-17

  preprintOpen access

  Background: Interictal cognitive and affective comorbidities in temporal lobe epilepsy (TLE) often remain refractory to seizure-directed therapies. We tested the causal role of ventral hippocampal CA1/subiculum (vCA1/Sub) hyperexcitability in social memory failure and anxiety-related behavior, and whether normalizing principal-cell excitability restores function. Methods: In pilocarpine-treated mice we combined blinded behavioral assays (social approach/discrimination, open field, olfaction), whole-cell recordings from mCherry-labeled vCA1/Sub principal neurons, alveus stimulation to assay synaptic inhibition/excitation, immunohistochemistry for parvalbumin (PV) and somatostatin (SST) interneurons, and chemogenetic control of excitability (hM3Dq in controls; hM4Di and KORD in epileptic mice). Missing behavioral outcomes were handled by multiple imputation with bootstrapping; pooled analyses used ANOVA, mixed-effects models, and logistic regression. Results: Epileptic mice showed preserved social approach but impaired social discrimination, with intact detection of social odors. Regular-spiking and bursting vCA1/Sub neurons exhibited depolarized resting membrane potential and reduced synaptically driven hyperpolarizations during alveus stimulation, indicating disinhibition; PV and SST interneuron densities were reduced in stratum oriens. Chemogenetic manipulation bidirectionally tuned excitability: bath CNO depolarized hM3Dq-expressing cells, whereas it hyperpolarized hM4Di-expressing cells by ~5 mV and decreased current-evoked spiking. In vivo, inhibiting vCA1/Sub principal cells (hM4Di or KORD activation) increased the probability of successful social discrimination in epileptic mice without altering investigation time; neither CNO nor salvinorin B affected unDREADDed animals. In the open field, epileptic mice displayed reduced center preference and high-velocity bouts; vCA1/Sub inhibition normalized center preference and movement toward control values. Center preference predicted social discrimination in DREADDed epileptic mice, linking anxiety-related behavior to vCA1/Sub excitability. Conclusions: vCA1/Sub hyperexcitability drives interictal social memory and anxiety-related deficits in chronic TLE. Reducing principal-cell excitability restores behavior despite interneuron loss, supporting a model in which ventral hippocampal output can be retuned to rescue cognition. These results nominate neuromodulation of vCA1/Sub as a strategy to improve quality of life in epilepsy.

  PublisherOA PDFDOI

• Normal or transitional? The evolution and properties of two type Ia supernovae in the Virgo cluster

  Astronomy and Astrophysics · 2025-12-16 · 1 citations

  articleOpen access

  Type Ia supernovae (SNe Ia) are among the most precise cosmological distance indicators used to study the expansion history of the Universe. The vast increase in SN Ia data due to large-scale astrophysical surveys has led to the discovery of a wide variety of SN Ia sub-classes, such as transitional and fast-declining SNe Ia. However, their distinct photometric and spectroscopic properties differentiate them from the population of normal SNe Ia such that their use as cosmological tools remains challenged. Here, we present a high-cadenced photometric and spectroscopic dataset of two SNe Ia, SNe 2020ue and 2020nlb, which were discovered in the nearby Virgo cluster of galaxies. Our study shows that SN 2020nlb is a normal SN Ia whose unusually red colour is intrinsic, arising from a lower photospheric temperature rather than interstellar reddening, providing clear evidence that colour diversity among normal SNe Ia can have a physical origin. In contrast, SN 2020ue has photometric properties, such as colour evolution and light curve decay rate, similar to those of transitional SNe. It is hence more spectroscopically aligned with normal SNe Ia. This is evident from spectroscopic indicators such as the pseudo-equivalent width of Si II lines. Thus, such SNe Ia, which lie photometrically at the edge of the standard normal SNe Ia range, may be missed in cosmological SNe Ia samples. Our results highlight that a spectroscopic analysis of SNe Ia around peak brightness is crucial for identifying intrinsic colour variations and constructing a more complete and physically homogeneous SN Ia sample for precision cosmology.

  PublisherDOI

• Normal or transitional? The evolution and properties of two type Ia supernovae in the Virgo cluster

  Lancaster EPrints (Lancaster University) · 2025-11-29

  preprintOpen access

  Type Ia supernovae (SNe Ia) are among the most precise cosmological distance indicators used to study the expansion history of the Universe. The vast increase of SN Ia data due to large-scale astrophysical surveys has led to the discovery of a wide variety of SN Ia sub-classes, such as transitional and fast-declining SNe Ia. However, their distinct photometric and spectroscopic properties differentiate them from the population of normal SNe Ia such that their use as cosmological tools remains challenged. Here, we present a high-cadenced photometric and spectroscopic dataset of two SNe Ia, SNe 2020ue and 2020nlb, which were discovered in the nearby Virgo cluster of galaxies. Our study shows that SN 2020nlb is a normal SN Ia whose unusually red color is intrinsic, arising from a lower photospheric temperature rather than interstellar reddening, providing clear evidence that color diversity among normal SNe Ia can have a physical origin. In contrast, SN 2020ue has photometric properties, such as color evolution and light-curve decay rate, similar to those of transitional SNe, spectroscopically it is more aligned with normal SNe Ia. This is evident from spectroscopic indicators such as the pseudo-equivalent width of \ion{Si}{II} lines. Thus, such SNe Ia that are photometrically at the edge of the standard normal SNe Ia range may be missed in cosmological SNe Ia samples. Our results highlight that spectroscopic analysis of SNe Ia around peak brightness is crucial for identifying intrinsic color variations and constructing a more complete and physically homogeneous SN Ia sample for precision cosmology.

  OA PDFDOI

• Chemogenetic Breakdown of the Dentate Gate Causes Seizures and Spatial Memory Deficits

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-14

  preprintOpen accessSenior authorCorresponding

  The dentate gyrus has often been posited to act as a gate that dampens highly active afferent input into the hippocampus. Effective gating is thought to prevent seizure initiation and propagation in the hippocampus and support learning and memory processes. Pathological changes to DG circuitry that occur in temporal lobe epilepsy (TLE) can increase DG excitability and impair its gating ability which can contribute to seizures and cognitive deficits. There is evidence that TLE pathologies and seizures may independently contribute to learning and memory deficits in TLE through distinct mechanisms. These two factors are difficult to untangle since TLE pathologies can drive seizures, and seizures can worsen TLE pathologies. Here we assessed whether chemogenetically increasing dentate granule cell (DGC) excitability was enough to break down the dentate gate in the absence of TLE pathologies. We found that increasing excitability specifically in DGCs caused seizures in non-epileptic mice. Importantly, due to the modulatory nature of DREADD effects, seizures were driven by intrinsic circuit activity rather than direct activation of DGCs. These seizures resulted in a spatial memory deficit when induced after training in the spatial object recognition task and showed stereotypical patterns of activity in miniscope calcium recordings. Our results provide direct support for the dentate gate hypothesis since seizures could be induced in non-epileptic animals by artificially degrading the dentate gate with chemogenetics in the absence of epilepsy pathologies.

  PublisherOA PDFDOI

• Double "acct": a distinct double-peaked supernova matching pulsational pair-instability models

  Lancaster EPrints (Lancaster University) · 2024-09-03

  preprintOpen access

  We present multi-wavelength data of SN2020acct, a double-peaked stripped-envelope supernova (SN) in NGC2981 at ~150 Mpc. The two peaks are temporally distinct, with maxima separated by 58 rest-frame days, and a factor of 20 reduction in flux between. The first is luminous (M$_{r}$ = -18.00 $\pm$ 0.02 mag), blue (g - r = 0.27 $\pm$ 0.03 mag), and displays spectroscopic signatures of interaction with hydrogen-free circumstellar material. The second peak is fainter (M$_{r}$ = -17.29 $\pm$ 0.03 mag), and spectroscopically similar to an evolved stripped-envelope SNe, with strong blended forbidden [Ca II] and [O II] features. No other known double-peak SN exhibits a light curve similar to that of SN 2020acct. We find the likelihood of two individual SNe occurring in the same star-forming region within that time to be highly improbable, while an implausibly fine-tuned configuration would be required to produce two SNe from a single binary system. We find that the peculiar properties of SN2020acct match models of pulsational pair instability (PPI), in which the initial peak is produced by collisions of shells of ejected material, shortly followed by a terminal explosion. Pulsations from a star with a 72 M$_{\odot}$ helium core provide an excellent match to the double-peaked light curve. The local galactic environment has a metallicity of 0.4 Z$_{\odot}$, a level where massive single stars are not expected retain enough mass to encounter the PPI. However, late binary mergers or a low-metallicity pocket may allow the required core mass. We measure the rate of SN 2020acct-like events to be $<3.3\times10^{-8}$ Mpc$^{-3}$ yr$^{-1}$ at z = 0.07, or <0.1% of the total core-collapse SN rate.

  OA PDFDOI

• Testing for Intrinsic Type Ia Supernova Luminosity Evolution at z>2 with JWST

  arXiv (Cornell University) · 2024-11-18

  preprintOpen access

  The James Webb Space Telescope} (JWST) is opening new frontiers of transient discovery and follow-up at high-redshift. Here we present the discovery of a spectroscopically confirmed Type Ia supernova (SN Ia; SN $2023$aeax) at $z=2.15$ with JWST, including a NIRCam multi-band light curve. SN $2023$aeax lands at the edge of traditional low-$z$ cosmology cuts because of its blue color (peak rest-frame $B-V\sim-0.3$) but with a normal decline rate ($\Delta m_{15}(B)\sim1.25$), and applying a fiducial standardization with the BayeSN model we find the SN $2023$aeax luminosity distance is in $\sim0.1\sigma$ agreement with $\Lambda$CDM. SN $2023$aeax is only the second spectroscopically confirmed SN Ia in the dark matter-dominated Universe at $z>2$ (the other is SN $2023$adsy), giving it rare leverage to constrain any potential evolution in SN Ia standardized luminosities. Similar to SN $2023$adsy ($B-V\sim0.8)$, SN $2023$aeax has a fairly extreme (but opposite) color, which may be due to the small sample size or a secondary factor, such as host galaxy properties. Nevertheless, the SN $2023$aeax spectrum is well-represented by normal low-$z$ SN Ia spectra and we find no definitive evolution in SN Ia standardization with redshift. Still, the first two spectroscopically confirmed $z>2$ SNe Ia have peculiar colors and combine for a $\sim1\sigma$ distance slope relative to $\Lambda$CDM, though in agreement with recent SN Ia cosmological measurements.

  PublisherOA PDF

• SN 2024ggi in NGC 3621: Rising Ionization in a Nearby, CSM-Interacting Type II Supernova

  arXiv (Cornell University) · 2024-04-29

  preprintOpen access

  We present UV/optical/NIR observations and modeling of supernova (SN) 2024ggi, a type II supernova (SN II) located in NGC 3621 at 7.2 Mpc. Early-time ("flash") spectroscopy of SN 2024ggi within +0.8 days of discovery shows emission lines of H I, He I, C III, and N III with a narrow core and broad, symmetric wings (i.e., IIn-like) arising from the photoionized, optically-thick, unshocked circumstellar material (CSM) that surrounded the progenitor star at shock breakout. By the next spectral epoch at +1.5 days, SN 2024ggi showed a rise in ionization as emission lines of He II, C IV, N IV/V and O V became visible. This phenomenon is temporally consistent with a blueward shift in the UV/optical colors, both likely the result of shock breakout in an extended, dense CSM. The IIn-like features in SN 2024ggi persist on a timescale of $t_{\rm IIn} = 3.8 \pm 1.6$ days at which time a reduction in CSM density allows the detection of Doppler broadened features from the fastest SN material. SN 2024ggi has peak UV/optical absolute magnitudes of $M_{\rm w2} = -18.7$ mag and $M_{\rm g} = -18.1$ mag that are consistent with the known population of CSM-interacting SNe II. Comparison of SN 2024ggi with a grid of radiation hydrodynamics and non-local thermodynamic equilibrium (nLTE) radiative-transfer simulations suggests a progenitor mass-loss rate of $\dot{M} = 10^{-2}$M$_{\odot}$ yr$^{-1}$ ($v_w$ = 50 km/s), confined to a distance of $r < 5\times 10^{14}$ cm. Assuming a wind velocity of $v_w$ = 50 km/s, the progenitor star underwent an enhanced mass-loss episode in the last ~3 years before explosion.

  PublisherOA PDFDOI

• Highlights From AES2020, a Virtual American Epilepsy Society Experience

  Epiliepsy currents/Epilepsy currents · 2021-05-16 · 2 citations

  articleOpen access

  Due to COVID-19 a live, in-person meeting was not possible for the American Epilepsy Society in 2020. An alternative, virtual event, the AES2020, was held instead. AES2020 was a great success with 4679 attendees from 70 countries. The educational content was outstanding and spanned the causes, treatments, and outcomes from epileptic encephalopathy to the iatrogenicity of epilepsy interventions to neurocognitive disabilities to the approach to neocortical epilepsies. New gene therapy approaches such as antisense oligonucleotide treatment for Dravet syndrome were introduced and neuromodulation devices were discussed. There were many other topics discussed in special interest groups and investigators' workshops. A highlight was having a Nobel prize winner speak about memory processing. Human intracranial electrophysiology contributes insights into memory processing and complements animal work. In a special COVID symposium, the impact of COVID on patients with epilepsy was reviewed. Telehealth has been expanded rapidly and may be well suited for some parts of epilepsy care. In summary, the epilepsy community was alive and engaged despite being limited to a virtual platform.

  PublisherDOI

• Functional NMDA receptors are expressed by human pulmonary artery smooth muscle cells

  Scientific Reports · 2021-04-15 · 22 citations

  articleOpen access

  N-methyl-D-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In the present study, we examined the expression of NMDA receptor subunit mRNA and protein in human pulmonary artery (HPA) by quantitative polymerase chain reaction (PCR), immunohistochemistry and immunoblotting. We demonstrate that both GluN1 and GluN2 subunit mRNAs are expressed in HPA. In addition, GluN1 and GluN2 (A-D) subunit proteins are expressed by human pulmonary artery smooth muscle cells (HPASMCs) in vitro and in vivo. These subunits localize on the surface of HPASMCs and form functional ion channels as evidenced by whole-cell patch-clamp electrophysiology and reduced phenylephrine-induced contractile responsiveness of human pulmonary artery by the NMDA receptor antagonist MK801 under hypoxic condition. HPASMCs also express high levels of serine racemase and vesicular glutamate transporter 1, suggesting a potential source of endogenous agonists for NMDA receptor activation. Our findings show HPASMCs express functional NMDA receptors in line with their effect on pulmonary vasoconstriction, and thereby suggest a novel therapeutic target for pharmacological modulations in settings associated with pulmonary vascular dysfunction.

  PublisherOA PDFDOI

• X-linked cellular mosaicism underlies age-dependent occurrence of seizure-like events in mouse models of CDKL5 deficiency disorder

  Neurobiology of Disease · 2020-11-13 · 40 citations

  articleOpen access

  CDKL5 deficiency disorder (CDD) is an infantile, epileptic encephalopathy presenting with early-onset seizures, intellectual disability, motor impairment, and autistic features. The disorder has been linked to mutations in the X-linked CDKL5, and mouse models of the disease recapitulate several aspects of CDD symptomology, including learning and memory impairments, motor deficits, and autistic-like features. Although early-onset epilepsy is one of the hallmark features of CDD, evidence of spontaneous seizure activity has only recently been described in Cdkl5-deficient heterozygous female mice, but the etiology, prevalence, and sex-specificity of this phenotype remain unknown. Here, we report the first observation of disturbance-associated seizure-like events in heterozygous female mice across two independent mouse models of CDD: Cdkl5 knockout mice and CDKL5 R59X knock-in mice. We find that both the prevalence and severity of this phenotype increase with aging, with a median onset around 28 weeks of age. Similar seizure-like events are not observed in hemizygous knockout male or homozygous knockout female littermates, suggesting that X-linked cellular mosaicism is a driving factor underlying these seizure-like events. Together, these findings not only contribute to our understanding of the effects of CDKL5 loss on seizure susceptibility, but also document a novel, pre-clinical phenotype for future therapeutic investigation.

  PublisherDOI

Recent grants

• Neuronal Circuit Mechanisms of Epileptogenesis

  NIH · $8.2M · 1999–2024

• NIH Grant R01NS032403

  NIH · $3.5M · 2013

• NIH Grant P01NS025630

  NIH · $4.0M · 1999

• Normal and Pathological Function of the Dentate Gyrus

  NIH · $6.1M · 2012–2027

• NIH Grant P30NS047321

  NIH · $4.8M · 2009

Frequent coauthors

• Hajime Takano

  Children's Hospital of Philadelphia

  73 shared

• David R. Lynch

  Children's Hospital of Philadelphia

  44 shared

• Fu‐Chun Hsu

  Children's Hospital of Philadelphia

  39 shared

• Akiva S. Cohen

  University of Pennsylvania

  26 shared

• Amy R. Brooks‐Kayal

  University of California, Davis

  23 shared

• John R. Huguenard

  Stanford University

  23 shared

• Robert J. DeLorenzo

  Virginia Commonwealth University

  21 shared

• David A. Prince

  Stanford University

  21 shared

Labs

• Epilepsy Research LabPI

Education

• Ph.D.

  Boston University

  1986