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Papers by Justin Rosenthal

Research paper thumbnail of Sequential Expression of Nicotinic Acetylcholine Receptor Subunits Supports Development and Plasticity of a Drosophila Central Synapse

The central nervous system (CNS) of animals is arguably one of the most sophisticated instruments... more The central nervous system (CNS) of animals is arguably one of the most sophisticated instruments designed by nature, and one its cardinal components is the postsynaptic specialization. Decades of studies on the cholinergic neuromuscular junction and the central glutamatergic synapses in vertebrate organisms has informed us of just how many factors are at play during postsynaptic development. However, despite its importance, the central cholinergic synapse is one system lacking the same knowledge base as the above models. The thesis work presented here was designed with the aim of understanding if and how nicotinic acetylcholine receptor (nAchR) activity at the postsynapse is used by a developing neuron to shape the structural and functional properties of the synapse and its dendrite arbor during normal periods of maturation. To this end, we employed the ventral lateral neuron (LNv) as a cellular model for Drosophila CNS development. This small group of cells are second-order projec...

Research paper thumbnail of Brain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling

Nature Communications

Lipid shuttling between neurons and glia contributes to the development, function, and stress res... more Lipid shuttling between neurons and glia contributes to the development, function, and stress responses of the nervous system. To understand how a neuron acquires its lipid supply from specific lipoproteins and their receptors, we perform combined genetic, transcriptome, and biochemical analyses in the developing Drosophila larval brain. Here we report, the astrocyte-derived secreted lipocalin Glial Lazarillo (GLaz), a homolog of human Apolipoprotein D (APOD), and its neuronal receptor, the brain-specific short isoforms of Drosophila lipophorin receptor 1 (LpR1-short), cooperatively mediate neuron-glia lipid shuttling and support dendrite morphogenesis. The isoform specificity of LpR1 defines its distribution, binding partners, and ability to support proper dendrite growth and synaptic connectivity. By demonstrating physical and functional interactions between GLaz/APOD and LpR1, we elucidate molecular pathways mediating lipid trafficking in the fly brain, and provide in vivo eviden...

Research paper thumbnail of Constructing and Tuning Excitatory Cholinergic Synapses: The Multifaceted Functions of Nicotinic Acetylcholine Receptors in Drosophila Neural Development and Physiology

Frontiers in Cellular Neuroscience

Nicotinic acetylcholine receptors (nAchRs) are widely distributed within the nervous system acros... more Nicotinic acetylcholine receptors (nAchRs) are widely distributed within the nervous system across most animal species. Besides their well-established roles in mammalian neuromuscular junctions, studies using invertebrate models have also proven fruitful in revealing the function of nAchRs in the central nervous system. During the earlier years, both in vitro and animal studies had helped clarify the basic molecular features of the members of the Drosophila nAchR gene family and illustrated their utility as targets for insecticides. Later, increasingly sophisticated techniques have illuminated how nAchRs mediate excitatory neurotransmission in the Drosophila brain and play an integral part in neural development and synaptic plasticity, as well as cognitive processes such as learning and memory. This review is intended to provide an updated survey of Drosophila nAchR subunits, focusing on their molecular diversity and unique contributions to physiology and plasticity of the fly neura...

Research paper thumbnail of Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development in Drosophila

Proceedings of the National Academy of Sciences

The construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrit... more The construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite development. The fundamental mechanisms underlying these processes are most often studied in glutamatergic central synapses in vertebrates. Whether the same principles apply to excitatory cholinergic synapses, such as those found in the insect central nervous system, is not known. To address this question, we investigated a group of projection neurons in the Drosophila larval visual system, the ventral lateral neurons (LNvs), and identified nAchRα1 (Dα1) and nAchRα6 (Dα6) as the main functional nicotinic acetylcholine receptor (nAchR) subunits in the larval LNvs. Using morphological analyses and calcium imaging studies, we demonstrated critical roles of these two subunits in supporting dendrite morphogenesis and synaptic transmission. Furthermore, our RNA sequencing analyses and endogenous tagging approach identified distinct transcriptional controls over the two subunits in the LNvs, ...

Research paper thumbnail of Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development

Construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite de... more Construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite development. The fundamental mechanisms underlying these processes are most often studied in glutamatergic central synapses in vertebrates. Whether the same principles apply to excitatory cholinergic synapses in the insect central nervous system (CNS) is not known. To address this question, we investigated Drosophila ventral lateral neurons (LNvs) and identified nAchRα1 (Dα1) and nAchRα6 (Dα6) as the main functional nicotinic acetylcholine receptor (nAchR) subunits in these cells. With morphological and calcium imaging studies, we demonstrated their distinct roles in supporting dendrite morphogenesis and synaptic transmission. Furthermore, our analyses revealed a transcriptional upregulation of Dα1 and downregulation of Dα6 during larval development, indicating a close association between the temporal regulation of nAchR subunits and synapse maturation. Together, our findings show transcri...

Research paper thumbnail of Time-lapse Live Imaging and Quantification of Fast Dendritic Branch Dynamics in Developing Drosophila Neurons

Journal of Visualized Experiments

Research paper thumbnail of Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

Cell Reports

Highlights d Cell-type-specific RNA-seq analyses identify activity modified transcripts d Activit... more Highlights d Cell-type-specific RNA-seq analyses identify activity modified transcripts d Activity induces the upregulation of LpR1 and LpR2 transcripts in larval LNvs d LpRs are required for LNv dendrite morphogenesis during development d Upregulation of LpRs supports neuronal adaptation to elevated activity

Research paper thumbnail of Sequential Expression of Nicotinic Acetylcholine Receptor Subunits Supports Development and Plasticity of a Drosophila Central Synapse

The central nervous system (CNS) of animals is arguably one of the most sophisticated instruments... more The central nervous system (CNS) of animals is arguably one of the most sophisticated instruments designed by nature, and one its cardinal components is the postsynaptic specialization. Decades of studies on the cholinergic neuromuscular junction and the central glutamatergic synapses in vertebrate organisms has informed us of just how many factors are at play during postsynaptic development. However, despite its importance, the central cholinergic synapse is one system lacking the same knowledge base as the above models. The thesis work presented here was designed with the aim of understanding if and how nicotinic acetylcholine receptor (nAchR) activity at the postsynapse is used by a developing neuron to shape the structural and functional properties of the synapse and its dendrite arbor during normal periods of maturation. To this end, we employed the ventral lateral neuron (LNv) as a cellular model for Drosophila CNS development. This small group of cells are second-order projec...

Research paper thumbnail of Brain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling

Nature Communications

Lipid shuttling between neurons and glia contributes to the development, function, and stress res... more Lipid shuttling between neurons and glia contributes to the development, function, and stress responses of the nervous system. To understand how a neuron acquires its lipid supply from specific lipoproteins and their receptors, we perform combined genetic, transcriptome, and biochemical analyses in the developing Drosophila larval brain. Here we report, the astrocyte-derived secreted lipocalin Glial Lazarillo (GLaz), a homolog of human Apolipoprotein D (APOD), and its neuronal receptor, the brain-specific short isoforms of Drosophila lipophorin receptor 1 (LpR1-short), cooperatively mediate neuron-glia lipid shuttling and support dendrite morphogenesis. The isoform specificity of LpR1 defines its distribution, binding partners, and ability to support proper dendrite growth and synaptic connectivity. By demonstrating physical and functional interactions between GLaz/APOD and LpR1, we elucidate molecular pathways mediating lipid trafficking in the fly brain, and provide in vivo eviden...

Research paper thumbnail of Constructing and Tuning Excitatory Cholinergic Synapses: The Multifaceted Functions of Nicotinic Acetylcholine Receptors in Drosophila Neural Development and Physiology

Frontiers in Cellular Neuroscience

Nicotinic acetylcholine receptors (nAchRs) are widely distributed within the nervous system acros... more Nicotinic acetylcholine receptors (nAchRs) are widely distributed within the nervous system across most animal species. Besides their well-established roles in mammalian neuromuscular junctions, studies using invertebrate models have also proven fruitful in revealing the function of nAchRs in the central nervous system. During the earlier years, both in vitro and animal studies had helped clarify the basic molecular features of the members of the Drosophila nAchR gene family and illustrated their utility as targets for insecticides. Later, increasingly sophisticated techniques have illuminated how nAchRs mediate excitatory neurotransmission in the Drosophila brain and play an integral part in neural development and synaptic plasticity, as well as cognitive processes such as learning and memory. This review is intended to provide an updated survey of Drosophila nAchR subunits, focusing on their molecular diversity and unique contributions to physiology and plasticity of the fly neura...

Research paper thumbnail of Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development in Drosophila

Proceedings of the National Academy of Sciences

The construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrit... more The construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite development. The fundamental mechanisms underlying these processes are most often studied in glutamatergic central synapses in vertebrates. Whether the same principles apply to excitatory cholinergic synapses, such as those found in the insect central nervous system, is not known. To address this question, we investigated a group of projection neurons in the Drosophila larval visual system, the ventral lateral neurons (LNvs), and identified nAchRα1 (Dα1) and nAchRα6 (Dα6) as the main functional nicotinic acetylcholine receptor (nAchR) subunits in the larval LNvs. Using morphological analyses and calcium imaging studies, we demonstrated critical roles of these two subunits in supporting dendrite morphogenesis and synaptic transmission. Furthermore, our RNA sequencing analyses and endogenous tagging approach identified distinct transcriptional controls over the two subunits in the LNvs, ...

Research paper thumbnail of Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development

Construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite de... more Construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite development. The fundamental mechanisms underlying these processes are most often studied in glutamatergic central synapses in vertebrates. Whether the same principles apply to excitatory cholinergic synapses in the insect central nervous system (CNS) is not known. To address this question, we investigated Drosophila ventral lateral neurons (LNvs) and identified nAchRα1 (Dα1) and nAchRα6 (Dα6) as the main functional nicotinic acetylcholine receptor (nAchR) subunits in these cells. With morphological and calcium imaging studies, we demonstrated their distinct roles in supporting dendrite morphogenesis and synaptic transmission. Furthermore, our analyses revealed a transcriptional upregulation of Dα1 and downregulation of Dα6 during larval development, indicating a close association between the temporal regulation of nAchR subunits and synapse maturation. Together, our findings show transcri...

Research paper thumbnail of Time-lapse Live Imaging and Quantification of Fast Dendritic Branch Dynamics in Developing Drosophila Neurons

Journal of Visualized Experiments

Research paper thumbnail of Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

Cell Reports

Highlights d Cell-type-specific RNA-seq analyses identify activity modified transcripts d Activit... more Highlights d Cell-type-specific RNA-seq analyses identify activity modified transcripts d Activity induces the upregulation of LpR1 and LpR2 transcripts in larval LNvs d LpRs are required for LNv dendrite morphogenesis during development d Upregulation of LpRs supports neuronal adaptation to elevated activity