Compartmentalized calcium dynamics in a C. elegans interneuron encode head movement
ABSTRACT The confinement of neuronal activity to specific subcellular regions is a mechanism for expanding the computational properties of neurons. Although the circuit organization underlying compart-mentalized activity has been studied in several systems 1–4 , its cellular basis is still unknown. Here we characterize compartmentalized activity in Caenorhabditis elegans RIA interneurons, which have multiple reciprocal connections to head motor neurons and receive input from sensory pathways. We show that RIA spatially encodes head movement on a subcellular scale through axonal compart-mentalization. This subcellular axonal activity is dependent on acetylcholine release from head motor neurons and is simulta-neously present and additive with glutamate-dependent globally synchronized activity evoked by sensory inputs. Postsynaptically, the muscarinic acetylcholine receptor GAR-3 acts in RIA to compartmentalize axonal activity through the mobilization of intracellular calcium stores. The compartmentalized activity func-tions independently of the synchronized activity to modulate locomotory behaviour. The 'wiring diagram' of the C. elegans nervous system allows the dissection of circuit function from single neurons to behavioural outputs 5,6 . RIA interneurons regulate navigation behaviours and occupy a key circuit position, receiving input from multiple sensory networks and showing reciprocal synaptic connections with head motor neurons (Fig. 1a) 5,7,8 . To characterize the properties of RIA, we expressed the genetically encoded calcium indicator GCaMP3 (ref. 9) under the RIA-specific glr-3 promoter 10 and performed calcium imaging with a microfluidic device in which semi-restrained trans-genic animals could bend their heads in the dorsal–ventral plane, allowing simultaneous monitoring of neural activity and head move-ments 11 . We stimulated the animals with alternating fluid streams of 3-methylbutan-1-ol (also known as isoamyl alcohol; IAA) and buffer, because IAA is detected by AWC olfactory neurons, one of the sensory neurons upstream of RIA and some of its major synaptic inputs 12 . We did not detect any prominent calcium response in the RIA cell body (Supplementary Fig. 1a). The single axon of RIA projects ventrally into the nerve cord, where it forms a hairpin loop, then enters and extends around the nerve ring, forming a near-complete circle (Fig. 1b). C. elegans normally lies on its side such that several distinct portions of the RIA axon lie in the same focal plane: the 'loop' (the ventrally directed hairpin loop), nrD and nrV (the dorsal and ventral segments of the RIA axon in the nerve ring, respectively) (Fig. 1b). Strikingly, we observed robust calcium dynamics in each of these axonal segments that seemed to be independent, and this axonal calcium activity was correlated with head movement (Fig. 1c, d and Supplementary Movie 1).
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ABSTRACT: Motion vision provides essential cues for navigation and course control as well as for mate, prey, or predator detection. Consequently, neurons responding to visual motion in a direction-selective way are found in almost all species that see. However, directional information is not explicitly encoded at the level of a single photoreceptor. Rather, it has to be computed from the spatio-temporal excitation level of at least two photoreceptors. How this computation is done and how this computation is implemented in terms of neural circuitry and membrane biophysics have remained the focus of intense research over many decades. Here, we review recent progress made in this area with an emphasis on insects and the vertebrate retina.Neuron 09/2011; 71(6):974-94. · 14.74 Impact Factor
Experimental Neurology 02/1966; 14(1):44-56. · 4.70 Impact Factor
Article: Muscarinic regulation of dendritic and axonal outputs of rat thalamic interneurons: a new cellular mechanism for uncoupling distal dendrites.[show abstract] [hide abstract]
ABSTRACT: Inhibition is crucial for sharpening the sensory information relayed through the thalamus. To understand how the interneuron-mediated inhibition in the thalamus is regulated, we studied the muscarinic effects on interneurons in the lateral posterior nucleus and lateral geniculate nucleus of the thalamus. Here, we report that activation of muscarinic receptors switched the firing pattern in thalamic interneurons from bursting to tonic. Although neuromodulators switch the firing mode in several other types of neurons by altering their membrane potential, we found that activation of muscarinic subtype 2 receptors switched the fire mode in thalamic interneurons by selectively decreasing their input resistance. This is attributable to the muscarinic enhancement of a hyperpolarizing potassium conductance and two depolarizing cation conductances. The decrease in input resistance appeared to electrotonically uncouple the distal dendrites of thalamic interneurons, which effectively changed the inhibition pattern in thalamocortical cells. These results suggest a novel cellular mechanism for the cholinergic transformation of long-range, slow dendrite- and axon-originated inhibition into short-range, fast dendrite-originated inhibition in the thalamus observed in vivo. It is concluded that the electrotonic properties of the dendritic compartments of thalamic interneurons can be dynamically regulated by muscarinic activity.Journal of Neuroscience 03/2001; 21(4):1148-59. · 7.11 Impact Factor