About

Carlos Aizenman is a Professor of Neuroscience and Brain Science at Brown University. His research interests encompass various aspects of neuroscience, including neural excitability, synaptic plasticity, multisensory integration, and neural development. His scientific work began during his undergraduate studies at Brown, where he investigated visual cortical synaptic plasticity in Mark Bear's laboratory. He completed his PhD at Johns Hopkins University under David Linden, focusing on plasticity of inhibitory inputs and intrinsic excitability of deep-cerebellar nuclear neurons. His postdoctoral research was conducted in Holly Cline's lab, where he combined his interests in the visual system with neural excitability regulation, a focus that continues in his current laboratory. Since joining Brown in 2004, Aizenman has contributed extensively to understanding neural development, excitability, and plasticity, with a particular emphasis on the visual system, multisensory processing, and neurodevelopmental disorders such as autism and fragile X syndrome.

Research topics

• Biology
• Computer Science
• Artificial Intelligence
• Neuroscience
• Genetics
• Cognitive psychology
• Cell biology
• Programming language
• Psychology
• Physics
• Human–computer interaction

Selected publications

• Synapse specific alterations of autophagy are a hallmark of Danon disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-15

  articleOpen access

  ABSTRACT Danon disease is a rare disorder caused by mutations in the LAMP2 gene, which encodes a lysosomal membrane protein key to the endolysosomal pathway and autophagy. Affected individuals show multisystemic alterations that include cardiomyopathy, skeletal muscle weakness, visual deficits and cognitive impairment. Here we establish a knockout LAMP2 line in Xenopus tropicalis that reproduces the characteristic cardiac activity, mobility impairments and vision deficits present in the disease. Damaged mitochondria were abundantly found in skeletal muscle fibers. LAMP2 mutant X. tropicalis detected light with a reduced preference for green wavelengths. Visual deficits were consistent with the finding of damaged mitochondria in the inner segment of rods but not in cones. Differences in autophagic flux were found in presynaptic terminals from photoreceptors and olfactory sensory neurons (OSNs), which establish the first synapse processing vision and olfaction, respectively. In wild-type animals autophagic shapes were observed in OSN terminals but were absent from photoreceptor ribbon synapses. In knockout LAMP2 tadpoles, autophagic organelles covered 7% of the OSN presynaptic terminal surface, a three-fold increase compared to photoreceptor terminals. These differences suggest that LAMP2 plays synapse-specific roles that could be an important determinant of the psychiatric manifestations present in Danon disease and support the use of LAMP2 X. tropicalis to shed new light on the pathological bases of this lysosomal storage disorder.

  PublisherOA PDFDOI

• Characterization of Na⁺currents regulating intrinsic excitability of optic tectal neurons

  Life Science Alliance · 2023-11-02

  articleOpen accessSenior authorCorresponding

  Developing neurons adapt their intrinsic excitability to maintain stable output despite changing synaptic input. The mechanisms behind this process remain unclear. In this study, we examined Xenopus optic tectal neurons and found that the expressions of Na v 1.1 and Na v 1.6 voltage-gated Na + channels are regulated during changes in intrinsic excitability, both during development and becsuse of changes in visual experience. Using whole-cell electrophysiology, we demonstrate the existence of distinct, fast, persistent, and resurgent Na + currents in the tectum, and show that these Na + currents are co-regulated with changes in Na v channel expression. Using antisense RNA to suppress the expression of specific Na v subunits, we found that up-regulation of Na v 1.6 expression, but not Na v 1.1, was necessary for experience-dependent increases in Na + currents and intrinsic excitability. Furthermore, this regulation was also necessary for normal development of sensory guided behaviors. These data suggest that the regulation of Na + currents through the modulation of Na v 1.6 expression, and to a lesser extent Na v 1.1, plays a crucial role in controlling the intrinsic excitability of tectal neurons and guiding normal development of the tectal circuitry.

  PublisherOA PDFDOI

• Early Developmental Exposure to Fluoxetine and Citalopram Results in Different Neurodevelopmental Outcomes

  Neuroscience · 2021-05-25 · 6 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Schooling in <i>Xenopus laevis</i> Tadpoles as a Way to Assess Their Neural Development

  Cold Spring Harbor Protocols · 2021 · 7 citations

  Senior authorCorresponding
  • Computer Science
  • Artificial Intelligence
  • Computer Science

  tadpoles show polarized schooling. Not only do tadpoles aggregate, they also swim in the same direction. Quantifying both aggregation and relative swim angle can give us an important measure of social behavior and sensory integration. Past iterations of these experiments have required the continued presence of an experimenter throughout the duration of each trial and relied on expensive software for subsequent data analysis. The instrument configuration and analysis protocol outlined here provide an automated method to assess schooling by delivering a series of timed vibratory stimuli to a group of tadpoles to induce swimming behavior and then controlling a camera to document their positions via still images. Both stimulus delivery and image acquisition are automated using the Python programming language. Analysis is done using ImageJ and custom Python scripts, which are provided in this protocol. The specific equipment configuration and scripts shown here provide one solution, but other equipment and custom scripts can be substituted.

  PublisherDOI

• Regulation of Na _v 1.6-mediated sodium currents underlie the homeostatic control of neuronal intrinsic excitability in the optic tectum of the developing <i>Xenopus laevis</i> tadpole

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-10-08

  preprintOpen accessSenior authorCorresponding

  ABSTRACT For individual neurons to function appropriately within a network that is undergoing synaptic reorganization and refinement due to developmental or experience-dependent changes in circuit activity, they must homeostatically adapt their intrinsic excitability to maintain a consistent output despite the changing levels of synaptic input. This homeostatic plasticity of excitability is particularly important for the development of sensory circuits, where subtle deficits in neuronal and circuit function cause developmental disorders including autism spectrum disorder and epilepsy. Despite the critical importance of this process for normal circuit development, the molecular mechanism by which this homeostatic control of intrinsic excitability is regulated is not fully understood. Here, we demonstrate that Xenopus optic tectal neurons express distinct fast, persistent and resurgent Na + currents. Here, we demonstrate that Xenopus optic tectal neurons express distinct fast, persistent and resurgent Na + currents. These are regulated with developmental changes in synaptic input, and homeostatically in response to changes in visual input. We show that expression of the voltage-gated Na + channel subtype Na v 1.6 is regulated with changes in intrinsic excitability, that blocking Na v 1.6 channels is sufficient to decrease intrinsic excitability. Furthermore, that upregulation of Na v 1.6 expression is necessary for experience-dependent increases in Na + currents and intrinsic excitability. Finally, by examining behaviors that rely on visual and multisensory integration, we extend these findings to show that tight regulation of Na + channel gene expression during a critical period of tectal circuit development is required for the normal functional development of the tectal circuitry.

  PublisherOA PDFDOI

• Author response: Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis

  2021-06-11

  peer-reviewOpen accessSenior author

  Chronic dysregulation of matrix-metalloproteinase 9, which is associated with some neurodevelopmental disorders, leads to local hyperconnectivity in the developing brain, resulting in altered sensory processing and increased seizure susceptibility.

  PublisherDOI

• Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis

  eLife · 2021 · 20 citations

  Senior authorCorresponding
  • Neuroscience
  • Biology
  • Cell biology

  tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

  PublisherDOI

• Decision letter: Microglial trogocytosis and the complement system regulate axonal pruning in vivo

  2020-10-13

  peer-reviewOpen access1st authorCorresponding
  PublisherDOI

• Behavioral assays to study neural development in Xenopus laevis tadpoles

  bioRxiv (Cold Spring Harbor Laboratory) · 2020-08-22 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Escape responses, orienting reflexes, and social behaviors in Xenopus laevis tadpoles have been well documented in the literature (Lee et al. 2010; Roberts et al. 2000; Simmons et al. 2004; Katz et al. 1981; Villinger and Waldman 2012). In this article, we describe several behavioral protocols that together allow researchers efficiently (in terms of financial cost and time investment) and effectively assess developmental abnormalities in pre-metamorphic Xenopus tadpoles.

  PublisherOA PDFDOI

• Role of matrix metalloproteinase-9 in neurodevelopmental disorders and experience-dependent plasticity in Xenopus tadpoles

  bioRxiv (Cold Spring Harbor Laboratory) · 2020-05-31 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 is also associated with neurodevelopmental disorders (ND). Here we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed after early exposure to valproic acid (VPA), a known teratogen associated with autism spectrum disorder in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

  PublisherOA PDFDOI

Recent grants

• Cellular Mechanisms of Multisensory Integration in the Developing Midbrain

  NIH · $1.6M · 2017–2022

• Cellular mechanisms underlying the development of visually-guided behavior

  NSF · $600k · 2014–2018

• NIH Grant R01EY019578

  NIH · $1.1M · 2013

• CAREER: Cellular determinants of visual system function and development

  NSF · $750k · 2008–2014

Frequent coauthors

• Arseny S. Khakhalin

  Bard College

  36 shared

• Wei Dong

  Southwest Medical University

  22 shared

• David J. Linden

  Discovery Institute

  16 shared

• Kara G. Pratt

  15 shared

• Eric J. James

  Brown University

  14 shared

• Carolina M Ramirez-Vizcarrondo

  Providence College

  14 shared

• Hollis T. Cline

  Scripps Research Institute

  13 shared

• Adrian C. Thompson

  John Brown University

  12 shared

Labs

• The Aizenman LabPI

  Not provided

Education

• B.S., Neuroscience

  Brown University

• Ph.D.

  Johns Hopkins

• Other

  Holly Cline's Lab