scholarly journals Rapid multi-directed cholinergic transmission in the central nervous system

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Santhosh Sethuramanujam ◽  
Akihiro Matsumoto ◽  
Geoff deRosenroll ◽  
Benjamin Murphy-Baum ◽  
J Michael McIntosh ◽  
...  

AbstractIn many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale ‘non-synaptic’ mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a ‘tripartite’ structure facilitates a ‘multi-directed’ form of transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of transmission.

Author(s):  
Santhosh Sethuramanujam ◽  
Akihiro Matsumoto ◽  
J. Michael McIntosh ◽  
Miao Jing ◽  
Yulong Li ◽  
...  

AbstractAcetylcholine (ACh) is a key neurotransmitter that plays diverse roles in many parts of the central nervous system, including the retina. However, assessing the precise spatiotemporal dynamics of ACh is technically challenging and whether ACh transmits signals via rapid, point-to-point synaptic mechanisms, or broader-scale ‘non-synaptic’ mechanisms has been difficult to ascertain. Here, we examined the properties of cholinergic transmission at individual contacts made between direction-selective starburst amacrine cells and downstream ganglion cells in the retina. Using a combination of electrophysiology, serial block-face electron microscopy, and two-photon ACh imaging, we demonstrate that ACh signaling bears the hallmarks of both non-synaptic and synaptic forms of transmission. ACh co-activates nicotinic ACh receptors located on the intersecting dendrites of pairs of ganglion cells, with equal efficiency (non-synaptic)— and yet retains the ability to generate rapid ‘miniature’ currents (∼1 ms rise times: synaptic). Fast cholinergic signals do not appear to depend on anatomically well-defined synaptic structures. We estimate that ACh spread is limited to ∼1-2 µm from its sites of release, which may help starbursts drive local direction-selective cholinergic responses in ganglion cell dendrites. Together, our results establish the functional architecture for cholinergic signaling at a central synapse and propose a novel motif whereby single presynaptic sites can co-transmit information to multiple neurons on a millisecond timescale.


1989 ◽  
Vol 147 (1) ◽  
pp. 457-470 ◽  
Author(s):  
JAMES W. TRUMAN ◽  
PHILIP F. COPENHAVER

Larval and pupal ecdyses of the moth Manduca sexta are triggered by eclosion hormone (EH) released from the ventral nervous system. The major store of EH activity in the latter resides in the proctodeal nerves that extend along the larval hindgut. At pupal ecdysis, the proctodeal nerves show a 90% depletion of stored activity, suggesting that they are the major release site for the circulating EH that causes ecdysis. Surgical experiments involving the transection of the nerve cord or removal of parts of the brain showed that the proctodeal nerve activity originates from the brain. Retrograde and anterograde cobalt fills and immunocytochemistry using antibodies against EH revealed two pairs of neurons that reside in the ventromedial region of the brain and whose axons travel ipsilaterally along the length of the central nervous system (CNS) and project into the proctodeal nerve, where they show varicose release sites. These neurons constitute a novel neuroendocrine pathway in insects which appears to be dedicated solely to the release of EH.


2018 ◽  
Vol 5 (1) ◽  
pp. 255-272 ◽  
Author(s):  
Olga A. Maximova ◽  
Alexander G. Pletnev

Flaviviruses are major emerging human pathogens on a global scale. Some flaviviruses can infect the central nervous system of the host and therefore are regarded as neurotropic. The most clinically relevant classical neurotropic flaviviruses include Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus. In this review, we focus on these flaviviruses and revisit the concepts of flaviviral neurotropism, neuropathogenicity, neuroinvasion, and resultant neuropathogenesis. We attempt to synthesize the current knowledge about interactions between the central nervous system and flaviviruses from the neuroanatomical and neuropathological perspectives and address some misconceptions and controversies. We hope that revisiting these neuropathological concepts will improve the understanding of flaviviral neuroinfections. This, in turn, may provide further guiding foundations for relevant studies of other emerging or geographically expanding flaviviruses with neuropathogenic potential, such as Zika virus and dengue virus, and pave the way for intelligent therapeutic strategies harnessing potentially beneficial, protective host responses to interfere with disease progression and outcome.


1962 ◽  
Vol 39 (1) ◽  
pp. 45-69
Author(s):  
G. M. HUGHES ◽  
L. TAUC

1. The organization of the central nervous system of Aplysia depilans has been investigated in whole animal and isolated ganglion preparations using mechanical and electrical stimulation. 2. Intracellular micro-electrodes have been used to record activity in nerve cells of the abdominal ganglia in situ. Some cells are spontaneously active and quite unaffected by mechanical stimulation, whereas others show varying degrees of responsiveness. Those which are unaffected may exhibit regular rhythmic activity or intermittent bursts which are intrinsic to the cells themselves but in other cases are due to synaptic input from other central neurones. 3. In isolated central nervous system preparations a special study of the pleural ganglion has revealed many types of cell with electrical activity similar to that shown in isolated abdominal ganglion preparations. A notable feature of the pleural ganglion cells was the large size of the excitatory post-synaptic potentials recorded in response to stimulation of pre-synaptic fibres. 4. Different types of branching of cells of the pleural ganglia were investigated. By observing the somatic potential it was possible to decide in which nerve a particular cell sent collateral branches and which nerves contained fibres affecting the cell synaptically. By this means it was clear that a large number of pathways connect the cerebral and pleural ganglia on each side. 5. A large number of direct pathways were found of nerve fibres passing through ganglia without any synapse. 6. Synaptic pathways varied in the number and intrinsic properties of the individual synapses along their route. Synapses between fibres in the nerves innervating the foot and parapodial lobes of the two sides were not as common as has been described for Ariolimax. 7. In general the results have shown a great variety in the extent to which afferent stimulation may affect the whole or part of the central nervous system. They have also revealed the great multiplicity in the pathways whereby this is achieved.


1971 ◽  
Vol 54 (2) ◽  
pp. 329-350
Author(s):  
T. MILLER ◽  
P. N. R. USHERWOOD

1. The heart of Periplaneta americana is segmentally innervated from the central nervous system by three types of neurone. Two of these types of neurones are neurosecretory; one type contains large granules, the other small granules. The segmental nerves are paired structures which join paired lateral cardiac nerve cords. Both types of neurosecretory neurone liberate their contents in the lateral cardiac nerve cords. The neurones with the small granules also synapse with the myocardium as well as with intrinsic cardiac neurones in the lateral cardiac nerve cords. The third type of neurone from the central nervous system is an ordinary efferent neurone and it synapses with the cardiac ganglion cells. 2. A heart chamber is associated with about six cardiac ganglion cells, three on either side. These send processes up and down the lateral cardiac nerve cord and make synaptic contact with the myocardium. 3. The myocardium is multiterminally and polyneuronally innervated, and electrical coupling between muscle fibres appears to be the rule. The fibres are spontaneously active and generate spike-like electrically excited responses. The timing of the electrically excited responses is influenced by the input from the cardiac ganglion cells which evoke a burst of synaptic potentials during diastole. 4. Control of the cockroach heart appears to be organized on three levels. The basic rhythm is myogenic. The timing of the contractions is influenced by inputs from the intrinsic cardiac ganglion cells possibly via a feedback mechanism involving the contractions of the heart muscle. Finally, the activities of the heart muscle and the cardiac ganglion cells are influenced by inputs from the central nervous system.


Author(s):  
Ikunobu Muramatsu ◽  
Takayoshi Masuoka ◽  
Junsuke Uwada ◽  
Hatsumi Yoshiki ◽  
Takashi Yazama ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Santhosh Sethuramanujam ◽  
Akihiro Matsumoto ◽  
Geoff deRosenroll ◽  
Benjamin Murphy-Baum ◽  
Claudio Grosman ◽  
...  

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22763-3


2021 ◽  
Vol 15 ◽  
Author(s):  
Fredy Cifuentes ◽  
Miguel Angel Morales

Here, we present and discuss the characteristics and properties of neurotransmitter segregation, a subtype of neurotransmitter cotransmission. We review early evidence of segregation and discuss its properties, such as plasticity, while placing special emphasis on its probable functional implications, either in the central nervous system (CNS) or the autonomic nervous system. Neurotransmitter segregation is a process by which neurons separately route transmitters to independent and distant or to neighboring neuronal processes; it is a plastic phenomenon that changes according to synaptic transmission requirements and is regulated by target-derived signals. Distant neurotransmitter segregation in the CNS has been shown to be related to an autocrine/paracrine function of some neurotransmitters. In retinal amacrine cells, segregation of acetylcholine (ACh) and GABA, and glycine and glutamate to neighboring terminals has been related to the regulation of the firing rate of direction-selective ganglion cells. In the rat superior cervical ganglion, segregation of ACh and GABA to neighboring varicosities shows a heterogeneous regional distribution, which is correlated to a similar regional distribution in transmission strength. We propose that greater segregation of ACh and GABA produces less GABAergic inhibition, strengthening ganglionic transmission. Segregation of ACh and GABA varies in different physiopathological conditions; specifically, segregation increases in acute sympathetic hyperactivity that occurs in cold stress, does not vary in chronic hyperactivity that occurs in hypertension, and rises in early ages of normotensive and hypertensive rats. Given this, we propose that variations in the extent of transmitter segregation may contribute to the alteration of neural activity that occurs in some physiopathological conditions and with age.


2019 ◽  
Vol 26 (20) ◽  
pp. 3754-3763 ◽  
Author(s):  
Raffaele Mancino ◽  
Massimo Cesareo ◽  
Alessio Martucci ◽  
Emiliano Di Carlo ◽  
Elena Ciuffoletti ◽  
...  

Recent literature agrees that neurodegenerative processes involve both the retina and the central nervous system, which are two strictly related anatomical structures. However, the causal mechanisms of this dual involvement are still uncertain. To date, anterograde transsynaptic neurodegeneration, triggered by retinal ganglion cells’ death, and retrograde transsynaptic neurodegeneration, induced by neurodegenerative processes of the central nervous system, has been considered the major possible causal mechanisms. The development of novel neuroimaging techniques has recently supported both the study of the central stations of the visual pathway as well as the study of the retina which is possibly an open window to the central nervous system.


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