About

Colenso Speer is an Associate Professor in the Department of Biology at the University of Maryland and serves as the Director of the Physiological Systems Concentration Area within the BISI Graduate Program. His research focuses on understanding the molecular and activity-dependent mechanisms that instruct neural circuit development, with particular emphasis on the logic of synaptic connectivity within neural circuits and how brain structure establishes brain function. Using the mammalian visual system as a model, he explores changes in synaptic connectivity and function across parallel neural pathways from the eyes to central brain targets. His work employs transgenic and molecular tools to label and manipulate specific neuronal subsets, alongside electrophysiological, optical recording, and high-resolution imaging techniques, including three-dimensional super-resolution fluorescence microscopy. He integrates high-performance computing approaches to analyze large datasets, aiming to uncover new biological insights into the development and plasticity of neural circuits for sensory perception.

Research topics

• Neuroscience
• Biology
• Computer science
• Computer vision
• Artificial intelligence

Selected publications

• Melanopsin regulates axonal translation underlying retinohypothalamic circuit assembly

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-23

  articleOpen accessSenior author

  Abstract Intrinsically photosensitive retinal ganglion cells (ipRGCs) influence visual system development via melanopsin before photoreceptor-mediated vision, but how melanopsin signaling contributes to ipRGC circuit assembly remains unknown. Here we show that melanopsin coordinates retinohypothalamic tract development by regulating local translation in developing ipRGC axons. Loss of melanopsin selectively disrupted local translation in axons without affecting somatic translation. The affected transcripts encoded cytoskeletal regulators, adhesion molecules, and trafficking proteins, and activity-dependent changes in translation were restricted to the period before eye-opening. Consistent with impaired axonal growth and synaptogenesis, Opn4 knockout mice showed reduced ipsilateral suprachiasmatic nucleus innervation and fewer retinohypothalamic synapses, while nanoscale synaptic molecular organization and microglial engulfment were unaffected. Reduced visual drive in Opn4 knockouts further altered developmental gene expression programs across the retina, suprachiasmatic nucleus, and lateral geniculate nucleus, with region-specific differences in expression timing. These findings identify melanopsin as a regulator of local axonal translation during early circuit development, linking sensory phototransduction to translational control mechanisms that guide retinohypothalamic tract assembly and postsynaptic target maturation.

  PublisherOA PDFDOI

• Eye-specific active zone clustering underlies synaptic competition in the developing visual system

  eLife · 2025-09-08

  articleOpen accessSenior author

  Abstract Spatially clustered synaptic inputs enable local dendritic computations important for learning, memory, and sensory processing. In the mammalian visual system, individual retinal ganglion cell (RGC) axons form clustered terminal boutons containing multiple active zones onto relay cell dendrites in the dorsal lateral geniculate nucleus (dLGN). This mature architecture arises through the addition of release sites, which strengthens selected afferents while weaker inputs are pruned. Following eye-opening, spontaneous activity and visual experience promote synaptic refinement and bouton clustering after binocular inputs have segregated. However, anatomical changes in release site addition and spatial patterning during earlier stages of eye-specific competition are not well understood. To investigate this, we examined the spatial organization of eye-specific active zones in wild type mice and a mutant line with disrupted cholinergic retinal waves. Using volumetric super-resolution single-molecule localization microscopy and electron microscopy, we found that individual retinogeniculate boutons begin forming multiple nearby presynaptic active zones during the first postnatal week. Both eyes generate these “multi-active-zone” (mAZ) inputs throughout refinement, but the dominant-eye forms more numerous mAZ contacts, each with more active zones and larger vesicle pools. At the height of competition, the non-dominant-eye projection adds many single active zone (sAZ) synapses. Mutants with abnormal cholinergic retinal waves still form mAZ inputs, but develop fewer sAZ synapses and show reduced synapse clustering in projections from both eyes. Together, these findings reveal activity-dependent, eye-specific differences in release site addition during synaptic competition in circuits essential for visual perception and behavior.

  PublisherDOI

• Eye-specific differences in active zone addition during synaptic competition in the developing visual system

  eLife · 2025-11-10

  articleOpen accessSenior author

  Spatially clustered synaptic inputs enable local dendritic computations important for learning, memory, and sensory processing. In the mammalian visual system, individual retinal ganglion cell axons form clustered terminal boutons containing multiple active zones onto relay cell dendrites in the dorsal lateral geniculate nucleus. This mature architecture arises through the addition of release sites, which strengthens selected afferents while weaker inputs are pruned. Following eye-opening, spontaneous activity and visual experience promote synaptic refinement and bouton clustering after binocular inputs have segregated. However, anatomical changes in release site addition and spatial patterning during earlier stages of eye-specific competition are not well understood. To investigate this, we examined the spatial organization of eye-specific active zones in wild-type mice and a mutant line with disrupted cholinergic retinal waves. Using volumetric super-resolution single-molecule localization microscopy and electron microscopy, we found that individual retinogeniculate boutons begin forming multiple nearby presynaptic active zones during the first postnatal week. Both eyes generate these ‘multi-active-zone’ (mAZ) inputs throughout refinement, but the dominant eye forms more numerous mAZ contacts, each with more active zones and larger vesicle pools. At the height of competition (postnatal day 4), the non-dominant-eye projection adds many single-active-zone synapses. Mutants with abnormal cholinergic retinal waves still form mAZ inputs but develop fewer synapses overall and show reduced synaptic clustering in projections from both eyes. Together, these findings reveal eye-specific differences in release site addition that correlate with axonal segregation outcomes during retinogeniculate refinement.

  PublisherDOI

• Author response: Eye-specific differences in active zone addition during synaptic competition in the developing visual system

  2025-11-10

  peer-reviewOpen accessSenior author
  PublisherDOI

• Author response: Eye-specific differences in active zone addition during synaptic competition in the developing visual system

  2025-10-24

  peer-reviewOpen accessSenior author
  PublisherDOI

• Author response: Eye-specific active zone clustering underlies synaptic competition in the developing visual system

  2025-09-08

  peer-reviewOpen accessSenior author

  Spatially clustered synaptic inputs enable local dendritic computations important for learning, memory, and sensory processing. In the mammalian visual system, individual retinal ganglion cell (RGC) axons form clustered terminal boutons containing multiple active zones onto relay cell dendrites in the dorsal lateral geniculate nucleus (dLGN). This mature architecture arises through the addition of release sites, which strengthens selected afferents while weaker inputs are pruned. Following eye-opening, spontaneous activity and visual experience promote synaptic refinement and bouton clustering after binocular inputs have segregated. However, anatomical changes in release site addition and spatial patterning during earlier stages of eye-specific competition are not well understood. To investigate this, we examined the spatial organization of eye-specific active zones in wild type mice and a mutant line with disrupted cholinergic retinal waves. Using volumetric super-resolution single-molecule localization microscopy and electron microscopy, we found that individual retinogeniculate boutons begin forming multiple nearby presynaptic active zones during the first postnatal week. Both eyes generate these “multi-active-zone” (mAZ) inputs throughout refinement, but the dominant-eye forms more numerous mAZ contacts, each with more active zones and larger vesicle pools. At the height of competition, the non-dominant-eye projection adds many single active zone (sAZ) synapses. Mutants with abnormal cholinergic retinal waves still form mAZ inputs, but develop fewer sAZ synapses and show reduced synapse clustering in projections from both eyes. Together, these findings reveal activity-dependent, eye-specific differences in release site addition during synaptic competition in circuits essential for visual perception and behavior.

  PublisherDOI

• Eye-specific differences in active zone addition during synaptic competition in the developing visual system

  eLife · 2025-10-24

  articleOpen accessSenior author

  Spatially clustered synaptic inputs enable local dendritic computations important for learning, memory, and sensory processing. In the mammalian visual system, individual retinal ganglion cell (RGC) axons form clustered terminal boutons containing multiple active zones onto relay cell dendrites in the dorsal lateral geniculate nucleus (dLGN). This mature architecture arises through the addition of release sites, which strengthens selected afferents while weaker inputs are pruned. Following eye-opening, spontaneous activity and visual experience promote synaptic refinement and bouton clustering after binocular inputs have segregated. However, anatomical changes in release site addition and spatial patterning during earlier stages of eye-specific competition are not well understood. To investigate this, we examined the spatial organization of eye-specific active zones in wild type mice and a mutant line with disrupted cholinergic retinal waves. Using volumetric super-resolution single-molecule localization microscopy and electron microscopy, we found that individual retinogeniculate boutons begin forming multiple nearby presynaptic active zones during the first postnatal week. Both eyes generate these “multi-active-zone” (mAZ) inputs throughout refinement, but the dominant-eye forms more numerous mAZ contacts, each with more active zones and larger vesicle pools. At the height of competition (postnatal day 4), the non-dominant-eye projection adds many single active zone (sAZ) synapses. Mutants with abnormal cholinergic retinal waves still form mAZ inputs, but develop fewer synapses overall and show reduced synaptic clustering in projections from both eyes. Together, these findings reveal eye-specific differences in release site addition that correlate with axonal refinement outcomes during retinogeniculate refinement.

  PublisherDOI

• Author response: Activity-dependent synapse clustering underlies eye-specific competition in the developing retinogeniculate system

  2024-12-16

  peer-reviewOpen accessSenior author

  Co-active synaptic connections are often spatially clustered to facilitate local dendritic computations underlying learning, memory, and basic sensory processing. In the mammalian visual system, retinal ganglion cell (RGC) axons converge to form clustered synaptic inputs that enable local signal integration in the dorsal lateral geniculate nucleus (dLGN) of the thalamus. While visual experience promotes retinogeniculate synapse clustering after eye-opening, the earliest events in cluster formation prior to visual experience are unknown. Here, using volumetric super-resolution single-molecule localization microscopy and eye-specific labeling of developing retinogeniculate synapses in mice, we show that synaptic clustering is eye-specific and activity-dependent during retinogeniculate refinement in the first postnatal week. We identified a subset of retinogeniculate synapses with multiple active zones that are surrounded by like-eye synapses and depleted of synapse clustering from the opposite eye. In mutant mice with disrupted spontaneous retinal wave activity, synapses with multiple active zones still form, but do not exhibit the synaptic clustering seen in controls. These results highlight a role for spontaneous retinal activity in regulating eye-specific synaptic clustering in circuits essential for visual perception and behavior.

  PublisherDOI

• Activity-dependent synapse clustering underlies eye-specific competition in the developing retinogeniculate system

  eLife · 2024-12-16

  preprintOpen accessSenior author

  Abstract Co-active synaptic connections are often spatially clustered to facilitate local dendritic computations underlying learning, memory, and basic sensory processing. In the mammalian visual system, retinal ganglion cell (RGC) axons converge to form clustered synaptic inputs that enable local signal integration in the dorsal lateral geniculate nucleus (dLGN) of the thalamus. While visual experience promotes retinogeniculate synapse clustering after eye-opening, the earliest events in cluster formation prior to visual experience are unknown. Here, using volumetric super-resolution single-molecule localization microscopy and eye-specific labeling of developing retinogeniculate synapses in mice, we show that synaptic clustering is eye-specific and activity-dependent during retinogeniculate refinement in the first postnatal week. We identified a subset of retinogeniculate synapses with multiple active zones that are surrounded by like-eye synapses and depleted of synapse clustering from the opposite eye. In mutant mice with disrupted spontaneous retinal wave activity, synapses with multiple active zones still form, but do not exhibit the synaptic clustering seen in controls. These results highlight a role for spontaneous retinal activity in regulating eye-specific synaptic clustering in circuits essential for visual perception and behavior.

  PublisherDOI

• Microanalytical Mass Spectrometry with Super-Resolution Microscopy Reveals a Proteome Transition During Development of the Brain’s Circadian Pacemaker

  Analytical Chemistry · 2023-10-04 · 9 citations

  articleOpen accessCorresponding

  During brain development, neuronal proteomes are regulated in part by changes in spontaneous and sensory-driven activity in immature neural circuits. A longstanding model for studying activity-dependent circuit refinement is the developing mouse visual system where the formation of axonal projections from the eyes to the brain is influenced by spontaneous retinal activity prior to the onset of vision and by visual experience after eye-opening. The precise proteomic changes in retinorecipient targets that occur during this developmental transition are unknown. Here, we developed a microanalytical proteomics pipeline using capillary electrophoresis (CE) electrospray ionization (ESI) mass spectrometry (MS) in the discovery setting to quantify developmental changes in the chief circadian pacemaker, the suprachiasmatic nucleus (SCN), before and after the onset of photoreceptor-dependent visual function. Nesting CE-ESI with trapped ion mobility spectrometry time-of-flight (TOF) mass spectrometry (TimsTOF PRO) doubled the number of identified and quantified proteins compared to the TOF-only control on the same analytical platform. From 10 ng of peptide input, corresponding to <∼0.5% of the total local tissue proteome, technical triplicate analyses identified 1894 proteins and quantified 1066 proteins, including many with important canonical functions in axon guidance, synapse function, glial cell maturation, and extracellular matrix refinement. Label-free quantification revealed differential regulation for 166 proteins over development, with enrichment of axon guidance-associated proteins prior to eye-opening and synapse-associated protein enrichment after eye-opening. Super-resolution imaging of select proteins using STochastic Optical Reconstruction Microscopy (STORM) corroborated the MS results and showed that increased presynaptic protein abundance pre/post eye-opening in the SCN reflects a developmental increase in synapse number, but not presynaptic size or extrasynaptic protein expression. This work marks the first development and systematic application of TimsTOF PRO for CE-ESI-based microproteomics and the first integration of microanalytical CE-ESI TimsTOF PRO with volumetric super-resolution STORM imaging to expand the repertoire of technologies supporting analytical neuroscience.

  PublisherOA PDFDOI

Recent grants

• A molecular connectomics platform for multi-scale analysis of activity-dependent synapse development and plasticity

  NIH · $2.2M · 2020–2025

Frequent coauthors

• Chenghang Zhang

  10 shared

• Hazen P. Babcock

  Harvard University

  8 shared

• Barbara Chapman

  University of California, Davis

  8 shared

• Xiaowei Zhuang

  Harvard University Press

  8 shared

• Tarlan Vatan

  University of Maryland, College Park

  6 shared

• Ronak Patel

  Janelia Research Campus

  4 shared

• Erik B. Bloss

  Jackson Laboratory

  4 shared

• Timothy J. Stasevich

  Colorado State University

  4 shared

Education

• Research Associate (postdoctoral) , Chemistry and Chemical Biology

  Harvard University

  2016

• Ph.D., Neuroscience

  University of California Davis

  2010

• B.S. Molecular Biosciences/Biotechnology

  Arizona State University

  2004