scholarly journals The Feeding Connectome: Convergence of Monosynaptic and Polysynaptic Sensory Paths onto Common Motor Outputs

2018 ◽  
Author(s):  
Anton Miroschnikow ◽  
Philipp Schlegel ◽  
Andreas Schoofs ◽  
Sebastian Hückesfeld ◽  
Feng Li ◽  
...  

AbstractLittle is known about the organization of central circuits by which external and internal sensory inputs act on motor outputs to regulate fundamental behaviors such as feeding. We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior ofDrosophilalarvae. The input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS, as defined by distribution patterns of their presynaptic sites. The output neurons consist of pharyngeal motor neurons, serotonergic modulatory neurons, and neuroendocrine neurons that target the ring gland, a key endocrine organ. Monosynaptic connections from a set of sensory synaptic compartments cover the motor and endocrine targets in overlapping domains. Polysynaptic routes can be superimposed on top of the monosynaptic connections, resulting in divergent sensory paths that converge on common motor outputs. A completely different set of sensory compartments is connected to the mushroom body calyx of the memory circuits. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths.

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anton Miroschnikow ◽  
Philipp Schlegel ◽  
Andreas Schoofs ◽  
Sebastian Hueckesfeld ◽  
Feng Li ◽  
...  

We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior of Drosophila larvae. Input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS. Output neurons consist of feeding motor, serotonergic modulatory and neuroendocrine neurons. Monosynaptic connections from a set of sensory synaptic compartments cover the motor, modulatory and neuroendocrine targets in overlapping domains. Polysynaptic routes are superimposed on top of monosynaptic connections, resulting in divergent sensory paths that converge on common outputs. A completely different set of sensory compartments is connected to the mushroom body calyx. The mushroom body output neurons are connected to interneurons that directly target the feeding output neurons. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths.


2018 ◽  
Vol 217 (9) ◽  
pp. 3127-3139 ◽  
Author(s):  
Xiu-Tang Cheng ◽  
Yu-Xiang Xie ◽  
Bing Zhou ◽  
Ning Huang ◽  
Tamar Farfel-Becker ◽  
...  

Despite widespread distribution of LAMP1 and the heterogeneous nature of LAMP1-labeled compartments, LAMP1 is routinely used as a lysosomal marker, and LAMP1-positive organelles are often referred to as lysosomes. In this study, we use immunoelectron microscopy and confocal imaging to provide quantitative analysis of LAMP1 distribution in various autophagic and endolysosomal organelles in neurons. Our study demonstrates that a significant portion of LAMP1-labeled organelles do not contain detectable lysosomal hydrolases including cathepsins D and B and glucocerebrosidase. A bovine serum albumin–gold pulse–chase assay followed by ultrastructural analysis suggests a heterogeneity of degradative capacity in LAMP1-labeled endolysosomal organelles. Gradient fractionation displays differential distribution patterns of LAMP1/2 and cathepsins D/B in neurons. We further reveal that LAMP1 intensity in familial amyotrophic lateral sclerosis–linked motor neurons does not necessarily reflect lysosomal deficits in vivo. Our study suggests that labeling a set of lysosomal hydrolases combined with various endolysosomal markers would be more accurate than simply relying on LAMP1/2 staining to assess neuronal lysosome distribution, trafficking, and functionality under physiological and pathological conditions.


Author(s):  
Feng Li ◽  
Jack Lindsey ◽  
Elizabeth C. Marin ◽  
Nils Otto ◽  
Marisa Dreher ◽  
...  

AbstractMaking inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory and activity regulation. Here we identify new components of the MB circuit in Drosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.


1994 ◽  
Vol 72 (1) ◽  
pp. 235-247 ◽  
Author(s):  
H. Namba ◽  
T. Nagayama ◽  
M. Hisada

1. Electrical stimulation of afferents innervating an exopodite causes a closing pattern of activity in the uropod motor neurons. In this reflex two distinct types of nonspiking local interneurons, posterolateral (PL) and anterolateral (AL) types, classified by their gross morphology and somata location, receive sensory inputs and control the motor output to the uropod. 2. In the sensory-motor pathway, the PL and AL nonspiking local interneurons formed opposing and parallel connections with uropod motor neurons. For example, the PL interneurons that excited the closer, reductor motor neuron by injecting depolarizing current received depolarizing postsynaptic potentials (PSPs), whereas the AL interneurons of the same output received hyperpolarizing PSPs. The PL interneurons that inhibited the reductor motor neuron received hyperpolarizing PSPs, whereas the AL interneurons of the similar output received depolarizing PSPs. 3. During fictive abdominal extension, induced by electrical stimulation of extension-evoking command fibers in the second-third abdominal connective, the uropod motor neurons show an opening pattern of activity that is opposite to the pattern elicited by sensory stimulation. Furthermore, sensory stimulation during ongoing fictive abdominal extension has little effect on the uropod motor neurons. 4. Except for the nonspiking local interneurons, the majority of other local circuit neurons, i.e., spiking local interneurons and ascending interneurons, are not driven by the descending inputs during abdominal extension. 5. A comparison of the responses of the nonspiking local interneurons to both sensory and descending inputs reveals that the majority of nonspiking local interneurons receive both inputs, but the sign of response to each is frequently opposite. This study suggests that the degree of excitability of two distinct types of PL and AL nonspiking local interneurons induced by sensory inputs changes depending on whether the crayfish is in a resting posture or is active with full extension of the abdomen. Ongoing abdominal extension in swimming or defensive crayfish would shift the gain of reflex pathways through the PL and AL interneurons, and motor response resulting from sensory inputs would be modulated.


1999 ◽  
Vol 81 (4) ◽  
pp. 1730-1740 ◽  
Author(s):  
Maria Ullström ◽  
David Parker ◽  
Erik Svensson ◽  
Sten Grillner

Neuropeptide-mediated facilitation and inhibition of sensory inputs and spinal cord reflexes in the lamprey. The effects of neuromodulators present in the dorsal horn [tachykinins, neuropeptide Y (NPY), bombesin, and GABAB agonists] were studied on reflex responses evoked by cutaneous stimulation in the lamprey. Reflex responses were elicited in an isolated spinal cord preparation by electrical stimulation of the attached tail fin. To be able to separate modulator-induced effects at the sensory level from that at the motor or premotor level, the spinal cord was separated into three pools with Vaseline barriers. The caudal pool contained the tail fin. Neuromodulators were added to this pool to modulate sensory inputs evoked by tail fin stimulation. The middle pool contained high divalent cation or low calcium Ringer to block polysynaptic transmission and thus limit the input to the rostral pool to that from ascending axons that project through the middle pool. Ascending inputs and reflex responses were monitored by making intracellular recordings from motor neurons and extracellular recordings from ventral roots in the rostral pool. The tachykinin neuropeptide substance P, which has previously been shown to potentiate sensory input at the cellular and synaptic levels, facilitated tail fin-evoked synaptic inputs to neurons in the rostral pool and concentration dependently facilitated rostral ventral root activity. Substance P also facilitated the modulatory effects of tail fin stimulation on ongoing locomotor activity in the rostral pool. In contrast, NPY and the GABAB receptor agonist baclofen, both of which have presynaptic inhibitory effects on sensory afferents, reduced the strength of ascending inputs and rostral ventral root responses. We also examined the effects of the neuropeptide bombesin, which is present in sensory axons, at the cellular, synaptic, and reflex levels. As with substance P, bombesin increased tail fin stimulation-evoked inputs and ventral root responses in the rostral pool. These effects were associated with the increased excitability of slowly adapting mechanosensory neurons and the potentiation of glutamatergic synaptic inputs to spinobulbar neurons. These results show the possible behavioral relevance of neuropeptide-mediated modulation of sensory inputs at the cellular and synaptic levels. Given that the types and locations of neuropeptides in the dorsal spinal cord of the lamprey show strong homologies to that of higher vertebrates, these results are presumably relevant to other vertebrate systems.


1995 ◽  
Vol 73 (5) ◽  
pp. 1912-1923 ◽  
Author(s):  
Y. V. Panchin ◽  
L. B. Popova ◽  
T. G. Deliagina ◽  
G. N. Orlovsky ◽  
Y. I. Arshavsky

1. The pteropod mollusk Clione limacina swims by rhythmical oscillations of two wings, and its spatial orientation during locomotion is determined by tail movements. The majority of neurons responsible for generation of the wing and tail movements are located in the pedal ganglia. On the other hand, the majority of sensory inputs that affect wing and tail movements project to the cerebral ganglia. The goal of the present study was to identify and characterize cerebropedal neurons involved in the control of the swimming central generator or motor neurons of wing and tail muscles. Cerebropedal neurons affecting locomotion-controlling mechanisms are located in the rostromedial (CPA neurons), caudomedial (CPB neurons), and central (CPC neurons) zones of the cerebral ganglia. According to their morphology and effects on pedal mechanisms, 10 groups of the cerebropedal neurons can be distinguished. 2. CPA1 neurons project through the ipsilateral cerebropedal connective to both pedal ganglia. Activation of a CPA1 by current injection resulted in speeding up of the locomotor rhythm and intensification of the firing of the locomotor motor neurons. 3. CPA2 neurons send numerous thin fibers into the ipsi- and contralateral pedal and pleural ganglia through the cerebropedal and cerebropleural connectives. They strongly inhibit the wing muscle motor neurons and, to a lesser extent, slow down the locomotor rhythm. 4. CPB1 neurons project through the contralateral cerebropedal connective to both pedal ganglia. They activate the locomotor generator. 5. CPB2 neurons also project, through the contralateral cerebropedal connective, to both pedal ganglia. They affect wing muscle motor neurons. 6. CPB3 neurons have diverse morphology: they project to the pedal ganglia either through the ipsilateral cerebropedal connective, or through the contralateral one, or through both of them. They affect putative motor neurons of the tail muscles. 7. CPC1, CPC2, and CPC3 neurons project through the ipsilateral cerebropedal connective to both pedal ganglia. They activate the locomotor generator. 8. CPC4 and CPC5 neurons project through the contralateral cerebropedal connective to the contralateral pedal ganglia. They activate the locomotor generator. 9. Serotonergic neurons were mapped in the CNS of Clione by immunohistochemical methods. Location and size of cells in two groups of serotonin-immunoreactive neurons in the cerebral ganglia appeared to be similar to those of CPA1 and CPB1 neurons. This finding suggests a possible mechanism for serotonin's ability to exert a strong excitatory action on the locomotor generator of Clione. 10. The role of different groups of cerebropedal neurons is discussed in relation to different forms of Clione's behavior in which locomotor activity is involved.


2012 ◽  
Vol 520 (10) ◽  
pp. 2185-2201 ◽  
Author(s):  
Nancy J. Butcher ◽  
Anja B. Friedrich ◽  
Zhiyuan Lu ◽  
Hiromu Tanimoto ◽  
Ian A. Meinertzhagen

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Feng Li ◽  
Jack W Lindsey ◽  
Elizabeth C Marin ◽  
Nils Otto ◽  
Marisa Dreher ◽  
...  

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory and activity regulation. Here we identify new components of the MB circuit in Drosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.


Author(s):  
Richard E. Passingham

The primate prefrontal cortex sits at the top of the sensory, motor, and outcome processing hierarchies of the neocortex. It transforms sensory inputs into motor outputs, determining the response that is appropriate given the current context and desired outcome. This transformation involves conditional rules. The dorsal prefrontal cortex supports the learning of behavioural sequences, where the next action is conditional on the previous one. The ventral prefrontal cortex supports associations between objects, where the choice of one object is conditional on the presence of another object. However, because hierarchical processing supports the extraction of abstract representations, the primate prefrontal cortex is able to represent conditional rules that are abstract, meaning that they apply irrespective of the specific inputs. The selective advantage is that by learning these rules, primates can solve new problems rapidly when they have the same conditional logic as prior problems. The human prefrontal cortex has the same fundamental organization as in other primates. The dorsal prefrontal cortex supports the understanding of sequences and the ventral prefrontal cortex supports the ability to learn semantic associations. Thus the human prefrontal cortex has co-opted and elaborated mechanisms that were present in ancestral primates. These mechanisms can be used for new ends. For example, words have been associated with objects so as to communicate with others. This means that to understand human intelligence it is necessary to take into account the fact that the abstract rules are transmitted verbally from one generation to another.


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