| 1. |
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| 2. |
- Enjin, Anders, et al.
(författare)
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Developmental disruption of recurrent inhibitory feedback results in compensatory adaptation in the Renshaw cell-motor neuron circuit
- 2017
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 37:23, s. 5634-5647
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Tidskriftsartikel (refereegranskat)abstract
- When activating muscles, motor neurons in the spinal cord also activate Renshaw cells, which provide recurrent inhibitory feedback to the motor neurons. The tight coupling with motor neurons suggests that Renshaw cells have an integral role in movement, a role that is yet to be elucidated. Here we used the selective expression of the nicotinic cholinergic receptor α2 (Chrna2) in mice to genetically target the vesicular inhibitory amino acid transporter (VIAAT) in Renshaw cells. Loss of VIAAT from Chrna2Cre-expressing Renshaw cells did not impact any aspect of drug-induced fictive locomotion in the neonatal mouse or change gait, motor coordination, or grip strength in adult mice of both sexes. However, motor neurons from neonatal mice lacking VIAAT in Renshaw cells received spontaneous inhibitory synaptic input with a reduced frequency, showed lower input resistance, and had an increased number of proprioceptive glutamatergic and calbindin-labeled putative Renshaw cell synapses on their soma and proximal dendrites. Concomitantly, Renshaw cells developed with increased excitability and a normal number of cholinergic motor neuron synapses, indicating a compensatory mechanism within the recurrent inhibitory feedback circuit. Our data suggest an integral role for Renshaw cell signaling in shaping the excitability and synaptic input to motor neurons.
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| 3. |
- Leão, Richardson Naves, et al.
(författare)
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OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons
- 2012
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 15:11, s. 1524-1530
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Tidskriftsartikel (refereegranskat)abstract
- The vast diversity of GABAergic interneurons is believed to endow hippocampal microcircuits with the required flexibility for memory encoding and retrieval. However, dissection of the functional roles of defined interneuron types has been hampered by the lack of cell-specific tools. We identified a precise molecular marker for a population of hippocampal GABAergic interneurons known as oriens lacunosum-moleculare (OLM) cells. By combining transgenic mice and optogenetic tools, we found that OLM cells are important for gating the information flow in CA1, facilitating the transmission of intrahippocampal information (from CA3) while reducing the influence of extrahippocampal inputs (from the entorhinal cortex). Furthermore, we found that OLM cells were interconnected by gap junctions, received direct cholinergic inputs from subcortical afferents and accounted for the effect of nicotine on synaptic plasticity of the Schaffer collateral pathway. Our results suggest that acetylcholine acting through OLM cells can control the mnemonic processes executed by the hippocampus.
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| 4. |
- Corthals, Kristina, et al.
(författare)
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Genetic atlas of hygro-and thermosensory cells in the vinegar fly Drosophila melanogaster
- 2023
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The ability of animals to perceive and respond to sensory information is essential for their survival in diverse environments. While much progress has been made in understanding various sensory modalities, the sense of hygrosensation, which involves the detection and response to humidity, remains poorly understood. In this study, we focused on the hygrosensory, and closely related thermosensory, systems in the vinegar fly Drosophila melanogaster to unravel the molecular profile of the cells of these senses. Using a transcriptomic analysis of over 37,000 nuclei, we identified twelve distinct clusters of cells corresponding to temperature-sensing arista neurons, humidity-sensing sacculus neurons, and support cells relating to these neurons. By examining the expression of known and novel marker genes, we validated the identity of these clusters and characterized their gene expression profiles. We found that each cell type could be characterized by a unique expression profile of ion channels, GPCR signaling molecules, synaptic vesicle cycle proteins, and cell adhesion molecules. Our findings provide valuable insights into the molecular basis of hygro- and thermosensation. Understanding the mechanisms underlying hygro- and thermosensation may shed light on the broader understanding of sensory systems and their adaptation to different environmental conditions in animals.
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| 5. |
- Enjin, Anders, et al.
(författare)
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Humidity Sensing in Drosophila
- 2016
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 26:10, s. 8-1352
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Tidskriftsartikel (refereegranskat)abstract
- Environmental humidity influences the fitness and geographic distribution of all animals [1]. Insects in particular use humidity cues to navigate the environment, and previous work suggests the existence of specific sensory mechanisms to detect favorable humidity ranges [2-5]. Yet, the molecular and cellular basis of humidity sensing (hygrosensation) remains poorly understood. Here we describe genes and neurons necessary for hygrosensation in the vinegar fly Drosophila melanogaster. We find that members of the Drosophila genus display species-specific humidity preferences related to conditions in their native habitats. Using a simple behavioral assay, we find that the ionotropic receptors IR40a, IR93a, and IR25a are all required for humidity preference in D. melanogaster. Yet, whereas IR40a is selectively required for hygrosensory responses, IR93a and IR25a mediate both humidity and temperature preference. Consistent with this, the expression of IR93a and IR25a includes thermosensory neurons of the arista. In contrast, IR40a is excluded from the arista but is expressed (and required) in specialized neurons innervating pore-less sensilla of the sacculus, a unique invagination of the third antennal segment. Indeed, calcium imaging showed that IR40a neurons directly respond to changes in humidity, and IR40a knockdown or IR93a mutation reduced their responses to stimuli. Taken together, our results suggest that the preference for a specific humidity range depends on specialized sacculus neurons, and that the processing of environmental humidity can happen largely in parallel to that of temperature.
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| 6. |
- Enjin, Anders
(författare)
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Humidity sensing in insects — from ecology to neural processing
- 2017
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Ingår i: Current Opinion in Insect Science. - : Elsevier BV. - 2214-5745. ; 24, s. 1-6
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Forskningsöversikt (refereegranskat)abstract
- Humidity is an omnipresent climatic factor that influences the fitness, reproductive behavior and geographic distribution of animals. Insects in particular use humidity cues to navigate the environment. Although the sensory neurons of this elusive sense were first described more than fifty years ago, the transduction mechanism of humidity sensing (hygrosensation) remains unknown. Recent work has uncovered some of the key molecules involved, opening up for novel approaches to study hygrosensory transduction. In this review, I will discuss this progress made toward understanding hygrosensation in insects.
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| 7. |
- Enjin, Anders, et al.
(författare)
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Identification of novel spinal cholinergic genetic subtypes disclose Chodl and Pitx2 as markers for fast motor neurons and partition cells
- 2010
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 518:12, s. 2284-2304
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Tidskriftsartikel (refereegranskat)abstract
- Spinal cholinergic neurons are critical for motor function in both the autonomic and somatic nervous systems and are affected in spinal cord injury and in diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Using two screening approaches and in situ hybridization, we identified 159 genes expressed in typical cholinergic patterns in the spinal cord. These include two general cholinergic neuron markers, one gene exclusively expressed in motor neurons and nine genes expressed in unknown subtypes of somatic motor neurons. Further, we present evidence that Chondrolectin (Chodl) is a novel genetic marker for putative fast motor neurons and that estrogen-related receptor b (ERRb) is a candidate genetic marker for slow motor neurons. In addition, we suggest paired-like homeodomain transcription factor 2 (Pitx2) as a marker for cholinergic partition cells.
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| 8. |
- Enjin, Anders, 1981-
(författare)
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Neural Control of Movement : Motor Neuron Subtypes, Proprioception and Recurrent Inhibition
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Movement is central for life, and all animals depend on accurate regulation of movement for purposeful behavior. There is great diversity of movements, ranging between simple and vital breathing movements to minute and subtle movements of the face used to communicate emotions. Consequently, motor neurons, which are the only route of central nervous system output, are essential for all motor behaviors. To control the many motor behaviors expressed by an animal, motor neurons are exposed to a large number and variety of modulating synaptic inputs and have evolved into subtypes with specific functions. In this thesis, motor neuron subtypes and the synaptic input to motor neurons from Renshaw cells and Ia afferents have been studied. Novel molecular markers that identify subtypes of motor neurons are described. Three markers, Chodl, Calca and ERRβ, have been used to study the degeneration of subtypes of motor neurons in a mouse model of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Another marker, 5-ht1d, has been used to record the electrophysiological character of gamma motor neurons. In mice that lack 5-ht1d, motor neurons develop with reduced proprioceptive input. Remarkably, these mice had fewer foot faults than control animals when challenged to cross a narrow beam suggesting that the amplitude of monosynaptic proprioceptive input to motor neurons is not essential for motor coordination. In a final set of experiments, genetic removal of vesicular transport of neurotransmitter from Renshaw cells suggest that Renshaw cells are not integral for motor circuit function or motor behaviors. However, they are involved in the development of motor circuits in the spinal cord. Together, this thesis provides novel molecular tools for studies of motor neuron subtypes and novel data regarding the development and function of spinal motor circuits.
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| 9. |
- Enjin, Anders, et al.
(författare)
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Sensorimotor function is modulated by the serotonin receptor 1d, a novel marker for gamma motor neurons
- 2012
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 49:3, s. 322-332
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Tidskriftsartikel (refereegranskat)abstract
- Gamma motor neurons (MNs), the efferent component of the fusimotor system, regulate muscle spindle sensitivity. Muscle spindle sensory feedback is required for proprioception that includes sensing the relative position of neighboring body parts and appropriately adjust the employed strength in a movement. The lack of a single and specific genetic marker has long hampered functional and developmental studies of gamma MNs. Here we show that the serotonin receptor 1d (5-ht1d) is specifically expressed by gamma MNs and proprioceptive sensory neurons. Using mice expressing GFP driven by the 5-ht1d promotor, we performed whole-cell patch-clamp recordings of 5-ht1d::GFP(+) and 5-ht1d::GFP(-) motor neurons from young mice. Hierarchal clustering analysis revealed that gamma MNs have distinct electrophysiological properties intermediate to fast-like and slow-like alpha MNs. Moreover, mice lacking 5-ht1d displayed lower monosynaptic reflex amplitudes suggesting a reduced response to sensory stimulation in motor neurons. Interestingly, adult 5-ht1d knockout mice also displayed improved coordination skills on a beam-walking task, implying that reduced activation of MNs by Ia afferents during provoked movement tasks could reduce undesired exaggerated muscle output. In summary, we show that 5-ht1d is a novel marker for gamma MNs and that the 5-ht1d receptor is important for the ability of proprioceptive circuits to receive and relay accurate sensory information in developing and mature spinal cord motor circuits.
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| 10. |
- Frank, Dominic D, et al.
(författare)
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Early Integration of Temperature and Humidity Stimuli in the Drosophila Brain
- 2017
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822. ; 27:15, s. 4-2388
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Tidskriftsartikel (refereegranskat)abstract
- The Drosophila antenna contains receptor neurons for mechanical, olfactory, thermal, and humidity stimuli. Neurons expressing the ionotropic receptor IR40a have been implicated in the selection of an appropriate humidity range [], but although previous work indicates that insect hygroreceptors may be made up by a "triad" of neurons (with a dry-, a cold-, and a humid-air-responding cell []), IR40a expression included only cold- and dry-air cells. Here, we report the identification of the humid-responding neuron that completes the hygrosensory triad in the Drosophila antenna. This cell type expresses the Ir68a gene, and Ir68a mutation perturbs humidity preference. Next, we follow the projections of Ir68a neurons to the brain and show that they form a distinct glomerulus in the posterior antennal lobe (PAL). In the PAL, a simple sensory map represents related features of the external environment with adjacent "hot," "cold," "dry," and "humid" glomeruli-an organization that allows for both unique and combinatorial sampling by central relay neurons. Indeed, flies avoided dry heat more robustly than humid heat, and this modulation was abolished by silencing of dry-air receptors. Consistently, at least one projection neuron type received direct synaptic input from both temperature and dry-air glomeruli. Our results further our understanding of humidity sensing in the Drosophila antenna, uncover a neuronal substrate for early sensory integration of temperature and humidity in the brain, and illustrate the logic of how ethologically relevant combinations of sensory cues can be processed together to produce adaptive behavioral responses. Frank et al. describe humid-air receptors in the fly antenna. Previous work identified dry-air receptors, and they now show that humid and dry cells converge with thermosensory neurons in the brain, creating a sensory map for environmental parameters. They also describe second-order neurons that sample multiple modalities for early integration.
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