scholarly journals Parallel Visual Circuitry in a Basal Chordate

2019 ◽  
Author(s):  
Matthew J. Kourakis ◽  
Cezar Borba ◽  
Angela Zhang ◽  
Erin Newman-Smith ◽  
Priscilla Salas ◽  
...  

A common CNS architecture is observed in all chordates, from vertebrates to basal chordates like the ascidian Ciona. Currently Ciona stands apart among chordates in having a complete larval CNS connectome. Starting with visuomotor circuits predicted by the Ciona connectome, we used expression maps of neurotransmitter use with behavioral assays and pharmacology to identify two parallel visuomotor circuits that are responsive to different components of visual stimuli. The first circuit is characterized by glutamatergic photoreceptors and responds to the direction of light. These photoreceptors project to cholinergic motor neurons, via two tiers of cholinergic interneurons. The second circuit is responsive to changes in ambient light and mediates an escape response. This circuit starts with novel GABAergic photoreceptors which project to GABAergic interneurons, and then to cholinergic interneurons shared with the first circuit. Our observations on neurotransmitter use and the behavior of larvae lacking photoreceptors indicate the second circuit is disinhibitory.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Matthew J Kourakis ◽  
Cezar Borba ◽  
Angela Zhang ◽  
Erin Newman-Smith ◽  
Priscilla Salas ◽  
...  

A common CNS architecture is observed in all chordates, from vertebrates to basal chordates like the ascidian Ciona. Ciona stands apart among chordates in having a complete larval connectome. Starting with visuomotor circuits predicted by the Ciona connectome, we used expression maps of neurotransmitter use with behavioral assays to identify two parallel visuomotor circuits that are responsive to different components of visual stimuli. The first circuit is characterized by glutamatergic photoreceptors and responds to the direction of light. These photoreceptors project to cholinergic motor neurons, via two tiers of cholinergic interneurons. The second circuit responds to changes in ambient light and mediates an escape response. This circuit uses GABAergic photoreceptors which project to GABAergic interneurons, and then to cholinergic interneurons. Our observations on the behavior of larvae either treated with a GABA receptor antagonist or carrying a mutation that eliminates photoreceptors indicate the second circuit is disinhibitory.


Author(s):  
Mor R. Alkaslasi ◽  
Zoe E. Piccus ◽  
Hanna Silberberg ◽  
Li Chen ◽  
Yajun Zhang ◽  
...  

AbstractIn vertebrates, motor control relies on cholinergic neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these neurons and their different functional roles in the adult remain to be defined. Here, we developed a targeted single nuclear RNA sequencing approach and used it to identify an array of cholinergic interneurons, visceral and skeletal motor neurons. Our data expose markers for distinguishing these classes of cholinergic neurons and their extremely rich diversity. Specifically, visceral motor neurons, which provide autonomic control, could be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor neurons was also reflected in our analysis with alpha, beta, and gamma subtypes clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.


1989 ◽  
Vol 256 (3) ◽  
pp. G540-G545 ◽  
Author(s):  
P. Holzer

Isolated segments of the guinea pig small intestine were used to examine the transmitter circuitry of the neural pathways subserving the ascending enteric reflex (AER) contraction of the circular muscle. Inflation of an intraluminal balloon provided the distension stimulus for the AER. The ascending contraction was reduced to 5% of its original amplitude by atropine and to 10% by hexamethonium, which indicates that cholinergic interneurons and cholinergic motor neurons constitute the main AER pathway. However, in the continued presence of atropine or hexamethonium for 60 min, the AER recovered to approximately 30% of its original amplitude. The atropine-resistant AER was blocked by hexamethonium and the tachykinin antagonist spantide [( D-Arg1,D-Trp7,9, Leu11]-substance P) suggesting that it involved cholinergic interneurons and tachykinin-utilizing motor neurons. The hexamethonium-resistant AER was abolished by atropine but left unaffected by spantide, suggesting the participation of as yet unidentified interneurons and cholinergic motor neurons. These findings demonstrate that the AER is mediated by multiple neural pathways with different transmitters and that adaptive interactions between these pathways take place after blockade of one of its neurotransmitters systems.


2002 ◽  
Vol 87 (4) ◽  
pp. 2190-2194 ◽  
Author(s):  
Enrico Bracci ◽  
Diego Centonze ◽  
Giorgio Bernardi ◽  
Paolo Calabresi

The striatum is the main recipient of dopaminergic innervation. Striatal projection neurons are controlled by cholinergic and GABAergic interneurons. The effects of dopamine on projection neurons and cholinergic interneurons have been described. Its action on GABAergic interneurons, however, is still unknown. We studied the effects of dopamine on fast-spiking (FS) GABAergic interneurons in vitro, with intracellular recordings. Bath application of dopamine elicited a depolarization accompanied by an increase in membrane input resistance (an effect that persisted in the presence of tetrodotoxin) and action-potential discharge. These effects were mimicked by the D1-like dopamine receptor agonist SKF38393 but not by the D2-like agonist quinpirole. Evoked corticostriatal glutamatergic synaptic currents were not affected by dopamine. Conversely, GABAergic currents evoked by intrastriatal stimulation were reversibly depressed by dopamine and D2-like, but not D1-like, agonists. Cocaine elicited effects similar to those of dopamine on membrane potential and synaptic currents. These results show that endogenous dopamine exerts a dual excitatory action on FS interneurons, by directly depolarizing them (through D1-like receptors) and by reducing their synaptic inhibition (through presynaptic D2-like receptors).


2019 ◽  
Vol 316 (1) ◽  
pp. G32-G44 ◽  
Author(s):  
Marcello Costa ◽  
Lauren J. Keightley ◽  
Lukasz Wiklendt ◽  
Timothy J. Hibberd ◽  
John W. Arkwright ◽  
...  

In the guinea pig distal colon, nonpropulsive neurally mediated motor patterns have been observed in different experimental conditions. Isolated segments of guinea pig distal colon were used to investigate these neural mechanisms by simultaneously recording wall motion, intraluminal pressure, and smooth muscle electrical activity in different conditions of constant distension and in response to pharmacological agents. Three distinct neurally dependent motor patterns were identified: transient neural events (TNEs), cyclic motor complexes (CMC), and distal colon migrating motor complexes (DCMMC). These could occur simultaneously and were distinguished by their electrophysiological, mechanical, and pharmacological features. TNEs occurred at irregular intervals of ~3s, with bursts of action potentials at 9 Hz. They propagated orally at 12 cm/s via assemblies of ascending cholinergic interneurons that activated final excitatory and inhibitory motor neurons, apparently without involvement of stretch-sensitive intrinsic primary afferent neurons. CMCs occurred during maintained distension and consisted of clusters of closely spaced TNEs, which fused to cause high-frequency action potential firing at 7 Hz lasting ~10 s. They generated periodic pressure peaks mediated by stretch-sensitive intrinsic primary afferent neurons and by cholinergic interneurons. DCMMCs were generated by ongoing activity in excitatory motor neurons without apparent involvement of stretch-sensitive neurons, cholinergic interneurons, or inhibitory motor neurons. In conclusion, we have identified three distinct motor patterns that can occur concurrently in the isolated guinea pig distal colon. The mechanisms underlying the generation of these neural patterns likely involve recruitment of different populations of enteric neurons with distinct temporal activation properties.


2002 ◽  
Vol 87 (3) ◽  
pp. 1234-1243 ◽  
Author(s):  
S. Yasumoto ◽  
E. Tanaka ◽  
G. Hattori ◽  
H. Maeda ◽  
H. Higashi

Many studies have shown dopamine (DA) to have a modulatory effect on neuronal excitability, which cannot be simply classified as excitatory or inhibitory in the neostriatum. To clarify whether the responses to DA (10–30 μM) are excitatory or inhibitory in the mouse medium spiny neurons, we examined the effects of DA agonists on the synchronous potential trajectory from the resting potential to the subthreshold potential. The DA-induced potential changes, which were estimated at the subthreshold potential (approximately −60 mV), were summarized as the combination of three kinds of responses: an initial hyperpolarization lasting approximately 1 min and a slow depolarization and/or hyperpolarization lasting more than 20 min. A D1-like receptor agonist, R(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF81297, 1 μM) mainly induced the initial hyperpolarization and slow depolarization. A D2-like receptor agonist, trans-(−)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g]quinoline hydrochloride (quinpirole, 1 μM), mainly induced the initial hyperpolarization and slow hyperpolarization. D1-like receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390, 1 μM) depressed both the initial hyperpolarization and slow depolarization. D2-like receptor antagonist sulpiride (1 μM) depressed all the DA-induced responses except for the slow depolarization. TTX (0.5 μM) abolished all the DA-induced responses. Bicuculline (20 μM) and atropine (1 μM) abolished the DA-induced initial hyperpolarization and slow depolarization, respectively. Eitherdl-2-amino-5-phosphonopentanoic acid (AP5; 100 μM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 μM) blocked both the initial hyperpolarization and slow depolarization. The application of exogenous glutamate (Glu) mimicked the initial hyperpolarization and slow depolarization. These results suggest that the initial hyperpolarization is mainly due to GABA release via the cooperative action of D1- and D2-like receptors and Glu receptors in GABAergic interneurons, whereas the slow depolarization is mediated by acetylcholine (ACh) release via the cooperative action of mainly D1-like receptors and Glu receptors in cholinergic interneurons. The potential oscillation was generated at the subthreshold level in a Ba2+-, AP5-, CNQX-, bicuculline-, and atropine-containing medium. The oscillation depressed after the addition of TTX, Co2+, or DA. In DA agonists, quinpirole rather than SKF81297 had a more depressive effect on the potential oscillation. These results indicate that the slow hyperpolarization is due to the suppression of noninactivating Na+-Ca2+ conductances via mainly D2-like receptors in the medium spiny neurons. In conclusion, the DA actions on the medium spiny neurons show a transient inhibition by the activation of D1- and D2-like receptors in mainly GABAergic interneurons and a tonic excitation and/or inhibition by the activation of mainly D1-like receptors in cholinergic interneurons and by the activation of mainly D2-like receptors in the medium spiny neurons, respectively.


2015 ◽  
Vol 146 (4) ◽  
pp. 307-321 ◽  
Author(s):  
Frans Vinberg ◽  
Teemu T. Turunen ◽  
Hanna Heikkinen ◽  
Marja Pitkänen ◽  
Ari Koskelainen

Sensory cells adjust their sensitivity to incoming signals, such as odor or light, in response to changes in background stimulation, thereby extending the range over which they operate. For instance, rod photoreceptors are extremely sensitive in darkness, so that they are able to detect individual photons, but remain responsive to visual stimuli under conditions of bright ambient light, which would be expected to saturate their response given the high gain of the rod transduction cascade in darkness. These photoreceptors regulate their sensitivity to light rapidly and reversibly in response to changes in ambient illumination, thereby avoiding saturation. Calcium ions (Ca2+) play a major role in mediating the rapid, subsecond adaptation to light, and the Ca2+-binding proteins GCAP1 and GCAP2 (or guanylyl cyclase–activating proteins [GCAPs]) have been identified as important mediators of the photoreceptor response to changes in intracellular Ca2+. However, mouse rods lacking both GCAP1 and GCAP2 (GCAP−/−) still show substantial light adaptation. Here, we determined the Ca2+ dependency of this residual light adaptation and, by combining pharmacological, genetic, and electrophysiological tools, showed that an unknown Ca2+-dependent mechanism contributes to light adaptation in GCAP−/− mouse rods. We found that mimicking the light-induced decrease in intracellular [Ca2+] accelerated recovery of the response to visual stimuli and caused a fourfold decrease of sensitivity in GCAP−/− rods. About half of this Ca2+-dependent regulation of sensitivity could be attributed to the recoverin-mediated pathway, whereas half of it was caused by the unknown mechanism. Furthermore, our data demonstrate that the feedback mechanisms regulating the sensitivity of mammalian rods on the second and subsecond time scales are all Ca2+ dependent and that, unlike salamander rods, Ca2+-independent background-induced acceleration of flash response kinetics is rather weak in mouse rods.


Author(s):  
Natalie M. Doig ◽  
J. Paul Bolam

The striatum (or caudate-putamen, or caudate nucleus and putamen in those species in which they are divided by the internal capsule) is the major division of the basal ganglia, a group of structures involved in a variety of processes, including movement and cognitive and mnemonic functions. The striatum consists of a population of principal neurons, the medium-sized, densely spiny neurons (MSNs)—accounting for up to 97% of all neurons depending on species—which are the projection neurons of the striatum, several populations of GABAergic interneurons, and a population of cholinergic interneurons. The principal afferents of the striatum are glutamatergic, are derived from the cortex and thalamus, and mainly innervate the spines of MSNs. The essential computation performed by the striatum is the decision about which MSNs will fire, the consequence of which is altered firing of basal ganglia output neurons, and hence the selection of the basal ganglia–associated behavior.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jhan-Jie Peng ◽  
Shih-Han Lin ◽  
Yu-Tzu Liu ◽  
Hsin-Chieh Lin ◽  
Tsai-Ning Li ◽  
...  

Overproduction of reactive oxygen species (ROS) is known to mediate glutamate excitotoxicity in neurological diseases. However, how ROS burdens can influence neural circuit integrity remains unclear. Here, we investigate the impact of excitotoxicity induced by depletion of Drosophila Eaat1, an astrocytic glutamate transporter, on locomotor central pattern generator (CPG) activity, neuromuscular junction architecture, and motor function. We show that glutamate excitotoxicity triggers a circuit-dependent ROS feedback loop to sculpt the motor system. Excitotoxicity initially elevates ROS, thereby inactivating cholinergic interneurons and consequently changing CPG output activity to overexcite motor neurons and muscles. Remarkably, tonic motor neuron stimulation boosts muscular ROS, gradually dampening muscle contractility to feedback-enhance ROS accumulation in the CPG circuit and subsequently exacerbate circuit dysfunction. Ultimately, excess premotor excitation of motor neurons promotes ROS-activated stress signaling that alters neuromuscular junction architecture. Collectively, our results reveal that excitotoxicity-induced ROS can perturb motor system integrity through a circuit-dependent mechanism.


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