Increased density and age‐related sharing of synapses at the cone to OFF bipolar cell synapse in the mouse retina

Simmons, Aaron B.; Camerino, Michael J.; Clemons, Mellisa R.; Sukeena, Joshua M.; Bloomsburg, Samuel; Borghuis, Bart G.; Fuerst, Peter G.

doi:10.1002/cne.24810

Cited by 5 publications

(5 citation statements)

References 46 publications

(76 reference statements)

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“…We were able to measure BC3bs at the dendrite point before branching, which is a smaller space than the soma and could be offset from the soma due to dendritic tiling. This would suggest that factors that mediate spacing of BCs could promote dendrite spacing but not soma spacing, consistent with the localization of DSCAM protein, which regulates OFF BC tiling, on the dendrite tips of these cells (Simmons et al, 2017; Simmons et al, 2020).…”

Section: Discusionmentioning

confidence: 58%

OFF bipolar cell density varies by subtype, eccentricity, and along the dorsal ventral axis in the mouse retina

Camerino

Engerbretson

Fife

et al. 2020

J of Comparative Neurology

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The neural retina is organized along central-peripheral, dorsal-ventral, and laminar planes. Cellular density and distributions vary along the central-peripheral and dorsalventral axis in species including primates, mice, fish, and birds. Differential distribution of cell types within the retina is associated with sensitivity to different types of damage that underpin major retinal diseases, including macular degeneration and glaucoma. Normal variation in retinal distribution remains unreported for multiple cell types in widely used research models, including mouse. Here we map the distribution of all known OFF bipolar cell (BC) populations and horizontal cells. We report significant variation in the distribution of OFF BC populations and horizontal cells along the dorsal-ventral and central-peripheral axes of the retina. Distribution patterns are much more pronounced for some populations of OFF BC cells than others and may correspond to the cell type's specialized functions.

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Section: Discusionmentioning

confidence: 58%

OFF bipolar cell density varies by subtype, eccentricity, and along the dorsal ventral axis in the mouse retina

Camerino

Engerbretson

Fife

et al. 2020

J of Comparative Neurology

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“…Second, we compared cells from retinas that lack the pro‐apoptotic gene Bax to those from WT littermates. Many cell types have elevated numbers in these Bax knockout (KO) retinas, including the rod bipolar cells (Simmons et al, 2019 ). The thickness of the ONL and OPL remains unchanged (Lee et al, 2011 ; Péquignot et al, 2003 ), however, suggesting that rod photoreceptor number is unaltered; indeed, we found that counts of rod photoreceptors do not significantly differ in the absence of Bax (WT: mean ± SEM = 7,625,975 ± 188,281, n = 3; KO: mean ± SEM = 7,913,681 ± 198,660, n = 3; p = 0.353).…”

Section: Resultsmentioning

confidence: 99%

Cell numbers, cell ratios, and developmental plasticity in the rod pathway of the mouse retina

2022

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The precise specification of cellular fate is thought to ensure the production of the correct number of neurons within a population. Programmed cell death may be an additional mechanism controlling cell number, believed to refine the proper ratio of pre‐ to post‐synaptic neurons for a given species. Here, we consider the size of three different neuronal populations in the rod pathway of the mouse retina: rod photoreceptors, rod bipolar cells, and AII amacrine cells. Across a collection of 28 different strains of mice, large variation in the numbers of all three cell types is present. The variation in their numbers is not correlated, so that the ratio of rods to rod bipolar cells, as well as rod bipolar cells to AII amacrine cells, varies as well. Establishing connectivity between such variable pre‐ and post‐synaptic populations relies upon plasticity that modulates process outgrowth and morphological differentiation, which we explore experimentally for both rod bipolar and AII amacrine cells in a mouse retina with elevated numbers of each cell type. While both rod bipolar dendritic and axonal arbors, along with AII lobular arbors, modulate their areal size in relation to local homotypic cell densities, the dendritic appendages of the AII amacrine cells do not. Rather, these processes exhibit a different form of plasticity, regulating the branching density of their overlapping arbors. Each form of plasticity should ensure uniformity in retinal coverage in the presence of the independent specification of afferent and target cell number.

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“…Unfortunately, these lines do not faithfully recapitulate the endogenous distribution of the HTR2A as has been seen with other BAC-transgenic mice (Matthaei, 2007). Despite this limitation, some groups have been used for HTR2-related research, such as electrophysiological studies (Weber et al, 2010), retina-related studies (Simmons et al, 2020)and circuitry-related research. The resultant data should be interpreted with caution since the distribution of HTR2A in the Htr2a BAC mouse lines are distinct from that of the endogenous receptor based on studies using receptor autoradiography (Pazos et al, 1985; Roth et al, 1987), immunohistochemistry (Willins et al, 1997a; Backstrom et al, 1997; Miner et al, 2003; Mengood et al, 1990), in situ hybridization (Wright et al, 1995) and our mouse lines.…”

Section: Discussionmentioning

confidence: 99%

A suite of engineered mice for interrogating psychedelic drug actions

Chiu,

Deutch,

Wang

et al. 2023

Preprint

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Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide a suite of engineered mice useful for clarifying the role of HTR2A and HTR2A-expressing neurons in psychedelic drug actions. We first generatedHtr2a-EGFP-CT-IRES-CreERT2 mice (CT:C-terminus) to independently identify both HTR2A-EGFP-CT receptors and HTR2A-containing cells thereby providing a detailed anatomical map of HTR2A and identifying cell types that express HTR2A. We also generated a humanizedHtr2amouse line and an additional constitutiveHtr2A-Cre mouse line. Psychedelics induced a variety of known behavioral changes in our mice validating their utility for behavioral studies. Finally, electrophysiology studies revealed that extracellular 5-HT elicited a HTR2A-mediated robust increase in firing of genetically-identified pyramidal neurons--consistent with a plasma membrane localization and mode of action. These mouse lines represent invaluable tools for elucidating the molecular, cellular, pharmacological, physiological, behavioral, and other actions of psychedelic drugsin vivo.

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Increased density and age‐related sharing of synapses at the cone to OFF bipolar cell synapse in the mouse retina

Cited by 5 publications

References 46 publications

OFF bipolar cell density varies by subtype, eccentricity, and along the dorsal ventral axis in the mouse retina

OFF bipolar cell density varies by subtype, eccentricity, and along the dorsal ventral axis in the mouse retina

Cell numbers, cell ratios, and developmental plasticity in the rod pathway of the mouse retina

A suite of engineered mice for interrogating psychedelic drug actions

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