Synaptic mechanisms in invertebrate pattern generation

Current Opinion in Neurobiology

Volumn 6, Issue 6, 1996, Pages 833-841

  Cropper, Elizabeth C ^a   Weiss, Klaudiusz R ^a  

^a MOUNT SINAI MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INVERTEBRATE; NONHUMAN; OSCILLATOR; PACEMAKER NERVE CELL; PHASE TRANSITION; PRIORITY JOURNAL; REVIEW; SYNAPTIC TRANSMISSION;

EID: 0030451541     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(96)80035-3     Document Type: Article

References (48)

1. Wang X, Rinzel j: Alternating and synchronous rhythms in reciprocally inhibitory model neurons. Neural Computation 1992,4:84-97.
2. Skinner F, Kopell N, Marder E: Mechanisms for oscillation and frequency control in reciprocally inhibitory model neural networks. J Comput Neurosci 1994, 1:69-87.
3. Sharp A, Skinner F, Marder E: Mechanisms of oscillation in dynamic clamp constructed two cell half-center circuits. J Neurophysiol 1996, 76:867-883. Skinner et al. {2] suggest that reciprocally inhibitory neurons can oscillate in four modes. To determine whether these results are physiologically relevant, Sharp et al. [3"] used the dynamic clamp technique to form reciprocally inhibitory synapses between pairs of real stomatogastric neurons (i.e. the gastric mill [GM] cells). In a typical experiment, the authors depolarize both cells above threshold such that their basal potentials and spike frequencies are similar. This level of constant current is maintained. Artificial inhibitory synapses are then added with the dynamic clamp. Although some neurons may oscillate under these conditions, GM neurons do not. Subsequently, the h currents are added and stable half-center oscillations are observed. To confirm the predictions of Skinner ef a/. [2], synaptic threshold was varied and plots of threshold versus period were generated. As predicted, an inverted U-shaped function was obtained. To identify the mechanisms of oscillation that are occurring in different regions of the curve, Sharp ef al. [3] decompressed the command voltages. Again, consistent with modeling data, the authors found that the GM cells utilize a synaptic escape mechanism at lower thresholds and a mixture of intrinsic escape and synaptic release at higher thresholds. In addition to altering synaptic threshold, these authors varied other synaptic properties (e.g. the time constant or synaptic conductance) and intrinsic conductances (e.g. the conductance or voltage-dependence of the h current) and describe changes in the period of the half-center oscillator. These manipulations simulate effects of modulators. For example, biogenic amines alter both the conductance and voltage dependence of the h current. As with varying threshold, changes in synaptic properties and intrinsic conductances produce effects that can depend on the initial mode of oscillation and can move the network from one mode to another.
4. K1. Thus, the cell that was originally the follower is now the initiator of activity. As it spikes, it inhibits its antagonist. The bursting mechanism in the leech model contains elements of both escape and release. Escape is promoted by the h current and by Ip. Release is promoted by decay of the synaptic currents. Modeling studies suggest, therefore, that distinctions between the four modes of transition described by Skinner ef a/. [2] are blurred in the leech heartbeat oscillator. What is clear, however, is that oscillations can be dominated by spike-mediated synaptic inhibition or by graded synaptic inhibition. Synaptic (S) mode oscillations appear to be closer to the oscillations of real neurons. The graded component of the synaptic transfer is large but inactivates. Sustained synaptic inhibition is provided by spike-mediated synaptic transmission.
5. + current and spike-mediated synaptic transmission.
6. 2+ current and about 20 times more graded inhibition. These results, therefore, confirm model predictions. Other results provide new insights into oscillatory mechanisms. For example, in the model, h currents had a strong influence on period: increasing the maximal conductance of the h current decreased period. Voltage-clamping results indicate, however, that increasing the period of the waveform increases the amount of h current present. Thus, h currents appear to provide negative feedback to any process that causes the oscillation to slow down. They may, therefore, be important for maintaining oscillations of fixed periods.
7. Arbas E, Calabrese R: Rate modification in the heartbeat central pattern generator of the medicinal leech. J Comp Physiol [A] 1984, 155:783-794.
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10. + current. The data suggest that the persistent Na+ current has a low threshold and contributes to the leak current [6]. (Effects of FMRFamide outside the timing oscillator are different.)
11. + conductance. Fast IPSPs are blocked by picrotoxin and are probably mediated by glutamate. Slow IPSPs are not blocked by picrotoxin, tetraethylammonium chloride, or scopolamine and are mediated by an unidentified neurotransmitter. Slow inhibition is probably particularly important for gastric rhythms that have a long cycle period.
12. Nusbaum MR Weimann JM, Golowasch J, Marder E: Presynaptic control of modulatory fibers by their neural network targets. J Neurosci 1992, 12:2706-2714.
13. Coleman MJ, Nusbaum MP: Functional consequences of compartmentalization of synaptic input J Neurosci 1994, 14:6544-6552.
14. Coleman MJ, Meyrand P, Nusbaum MP: A switch between two modes of synaptic transmission mediated by presynaptic inhibition. Nature 1995, 378:502-505. The gastric rhythm of the crab is generated by a subset of stomatogastric (STG) neurons and is influenced by the activity of projection neurons. The modulatory commissural neuron 1 (MCN1) is one such neuron. Specifically, the MCN1 neuron excites two neurons active during the gastric mill rhythm that constitute a half-center oscillator: the lateral gastric neuron (LG) and interneuron 1 (Int1). LG, in turn, presynaptically inhibits MCN1. Although the MCN1 excites both LG and Int1, tonic MCN1 stimulation elicits a pattern in which the activity of the LG neurons alternates with that of Int1. In this study, the authors characterize mechanisms that are likely to be important in producing this oscillatory behavior and suggest a heuristic model of how the network operates (see text and Figure 2a).
15. Katz PS, Getting PA, Frost WN: Dynamic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit Nature 1994, 367:729-731.
16. Frost W, Katz P: Single neuron control over a complex motor program. J Neurobiol 1996, 93:422-426. The authors characterize a neuron, the dorsal ramp intemeuron (DRI), that is important for the initiation of escape swimming in Tritonia. In reduced Trltonia preparations, fictive swimming can be elicited by extracellular stimulation of peripheral nerves such as pedal nerve 3. Nerve stimulation elicits rhythmic activity in a number of neurons, including those that constitute the swimming CPG. The authors show first, that stimulation of DRI will elicit rhythmic activity in CPG interneurons, thus DRI is 'sufficient' for eliciting motor programs, and second, that rhythmic activity elicited by stimulation of pedal nerve 3 ceases if DRI is inhibited, thus DRI is 'necessary' for rhythmic activity. The DRI neuron is, therefore, classified as a command neuron.
17. Katz P, Frost W: Intrinsic neuromodulation in the Tritonia swim CPG: the serotonergic dorsal swim interneurons act presynaptically to enhance transmitter release from intemeuron C2. J Neurosci 1995, 15:6035-6045. Examines synaptic connections between the dorsal swim interneurons (DSIs) and two types of follower neurons: C2 and a DFN. C2 is part of the CPG for escape swimming, and the DFNs are efferent dorsal flexion neurons. Previous studies had indicated that the DSIs are immunopositive for serotonin and that they produce three types of effects on followers: a fast EPSP followed by a prolonged slow EPSP, and a neuromodulatory effect on C2 synapses with other CPG elements and efferent flexion neurons. This paper presents pharmacological data and the results of occlusion experiments that suggest that all three types of actions of the DSIs are indeed mediated by serotonin.
18. Getting P: Emerging principles governing the operation of neural networks. Annu Rev Neurosci 1989, 12:185-204.
19. Jing J, Gillette R: Neuronal elements that mediate escape swimming and suppress feeding behavior in the predatory sea slug Pleurobranchaea. J Neurophysiol 1995, 74:1900-1910.
20. Johnson B, Peck J, Harris-Warrick R: Distributed amine modulation of graded chemical transmission in the pyloric network of the lobster stomatogastric ganglion. J Neurophysiol 1995, 74:437-452. In this study, the effects of the amines dopamine, octopamine, and serotonin on the pyloric network are investigated. Each amine elicits a distinctive motor pattern when exogenously applied. The effects of these amines on the graded synaptic strengths of the six major cell types of the pyloric network are characterized. Under control conditions, most graded chemical synapses are weak or nonfunctional. In the presence of modulators, some synaptic connections are strengthened, whereas others were weakened or abolished. The authors suggest that modulators are probably critical for normal pyloric activity because they not only quantitatively change synaptic gain but also qualitatively abolish and create functional synapses.
21. Katz P: Intrinsic and extrinsic neuromodulation of motor circuits. Curr Opin Neurobiol 1995, 5:799-808.
22. McPherson D, Blankenship J: Neural control of swimming in Aplysia brasiliana. III. Serotonergic modulatory neurons. J Neurophysiol 1991, 66:1366-1379.
23. Satterlie R, Norekian TP, Jordan S, Kazilek CJ: Serotonergic modulation of swimming speed in the pteropod mollusc Clione limacina, I. Serotonin immunoreactivity in the central nervous system and wings. J Exp Biol 1995, 198:895-904. Immunocytochemical techniques are used to identify serotonin-containing neurons in Clione limacina. Immunoreactive somata are found in the cerebral and pedal ganglia. Three clusters of neurons that are probably important for modulating swimming behavior are described and are studied in subsequent papers [24,25].
24. Satterlie R: Serotonergic modulation of swimming speed in the pteropod mollusc Clione limacina. II. Peripheral modulatory neurons. J Exp Biol 1995, 198:905-916. The author reports on a group of serotonin-immunopositive cells in the pedal ganglion of Clione. These neurons, the Pd-Sw cells, appear to play a functional role similar to that of the POP (parapodial opener phase) neurons in Aplysia brasiliana [22]. When the Pd-Sw neurons are stimulated in a swimming preparation, increases are observed in the junctional potentials of slow twitch muscles and in the strength of wing contractions. Stimulation of the Pd-SW neurons does not, however, influence swim frequency or produce detectable central effects in swim interneurons or swim motor neurons.
25. Satterlie R, Norekian P: Serotonergic modulation of swimming speed in the pteropod mollusc Clione limacina. III. Cerebral neurons. J Exp Biol 1995, 198:917-930. The authors examined two clusters of serotonin-immunoreactive neurons in the cerebral ganglion of Clione. One of these clusters is located towards the anterior side of the cerebral commissure (Cr-SA cells), the second cluster is to the posterior side (Cr-SP cells). In contrast to the Pd-Sw cells [24], both groups of cerebral neurons exert central effects; they produce an increase in swim frequency and depolarize swim interneurons. In addition, the Cr-SA and Cr-SP cells both exert excitatory effects on the neurons that are recruited during fast swimming, namely, type 12 interneurons and general excitor motor neurons. The synaptic actions of the two groups of cerebral neurons do not, however, appear to be identical. The time course of action of the Cr-SA cells did not greatly outlast the duration of spike activity, whereas that of the Cr-SP neurons typically outlasted burst duration.
26. Arshavsky Yl, Deliagina TG, Orlovsky GN, Panchin Y.V., Popova LB: Interneurons mediating the escape reaction of the marine mollusc Clione limacina. J Exp S/o/1992, 164:307-314.
27. Panchin Y.V. Popova LB, Deliagina TG, Orlovsky GN, Arshavsky Yl: Control of locomotion in marine mollusk Clione limacina. VIII. Cerebropedal neurons. J Neurophysiol 1995, 73:1912-1923. Identification of the cerebropedal neurons that control the swimming CPG in Clione. These neurons are divided into three general groups: CPA, CPB, and CPC. CPA1, CPB1, CPC1, CPC2, CPC3, CPC4, and CPC5 neurons speed up or activate the swimming CPG. At least some of the CPA1 and CPB1 cells are serotonergic and are probably the same neurons described by Satterlie and co-workers [23,25]. In addition to neurons that exert excitatory effects on the locomotory CPG, this paper describes neurons (e.g. the CPA2 neurons) that strongly inhibit wing motor neurons and, to a lesser extent, slow down the locomotor rhythm. The behavioral role of these neurons has not yet been determined.
28. Panchin YV, Arshavsky Yl, Deliagina TG, Popova LB, Orlovsky GN: Control of locomotion in marine mollusk Clione limacina. IX. Neuronal mechanisms of spatial orientation. J Neurophysiol 1995, 73:1924-1937. The authors provide further evidence that the CPA1 and CPB1 neurons described above [27] are activated when preparations are tilted or when statocyst receptor cells (SRCs) are electrically stimulated. Thus, these neurons are probably important for maintaining spatial orientation. Interestingly, it appears that activity of the SRCs can itself be modulated. The CPC1 cells exert excitatory effects on some SRCs but inhibitory effects on others. Central influences may, therefore, allow changes in spatial orientation to be made in a behaviorally appropriate manner.
29. Yeoman MS, Pieneman AW, Ferguson GP, Ter Maat A, Benjamin P: Modulatory role for the serotonergic cerebral giant cells in the feeding system of the snail, Lymnaea. I. Fine wire recording in the intact animal and pharmacology. J Neurophysiol 1994, 72:1357-1371.
30. Yeoman MS, Pieneman AW, Ferguson GP, Ter Maat A, Benjamin P: Modulatory role for the serotonergic cerebral giant cells in the feeding system of the snail, Lymnaea. II. Photoinactivation. J Neurophysiol 1994, 72:1372-1382.
31. Yeoman M, Brierley M, Benjamin P: Central pattern generator interneurons are targets for the modulatory serotonergic cerebral giant cells in the feeding system of Lymnaea. J Neurophysiol 1996, 75:11 -25. Studies such as those described in [29,30] have suggested that the cerebral giant cells (CGCs) modulate feeding behavior in Lymnaea. Until recently, however, direct effects of serotonergic neurons on the feeding CPG had not been studied. The authors address this issue. They show that the CGCs have a gating/enabling function in the generation of the feeding motor pattern since a minimum level of CPG activity must be maintained to support slow oscillator (SO)-driven fictive feeding (i.e. the CPGs must fire at about 7 spikes min-1). In addition, the CGCs may have a modulatory role in controlling the frequency of feeding when they fire in the 7-40 spikes min-1 range. These effects may be mediated by interactions with a number of different cell types, such as the SO neuron and N1, N2, and N3 interneurons. In addition, endogenous properties of a group of N1 neurons (the N1Ms) and N2 neurons (the N2vs) may be altered by CGC activity.
32. Yeoman MS, Vehovszky A, Elliot CJH, Benjamin P: Novel interneuron having hybrid modulatory-central pattern generator properties in the feeding system of the snail, Lymnaea stagnalis. J Neurophysiol 1995, 73:112-124. In reduced Lymnaea preparations, most feeding patterns are elicited by stimulating the SO (slow oscillator) neuron since it drives feeding rhythms at a physiological rate. The SO neuron is classified as 'modulatory1 since it is not necessary for rhythmic activity. The authors identify a new subclass of N1 interneurons, the N1Ls (lateral N1s) that can also elicit rhythmic activity in reduced preparations. When fictive feeding is elicited by sucrose application to semi-intact preparations, SO and N1L appear to be activated in parallel.
33. Morris B, Coleman M, Nusbaum M: Pyloric motor pattern modification by a newly identified projection neuron in the crab stomatogastric nervous system. J Neurophysiol 1996, 75:97-108. In a number of studies, neurotransmitters have been exogenously applied to the crustacean stomatogastric nervous system (STNS). To characterize the physiological relevance of the different types of input, relevant projection neurons are now being identified and their interactions with pattern-generating networks investigated. This work has led to the idea that the STNS is the target of a large number of projection neurons. Some of these inputs may use classical transmitters with rapid actions that can change rhythmic motor patterns on a cycle-by-cycle basis. Other inputs use transmitters that produce more long-lasting changes in motor patterns. Modulatory neurons that have been the subject of recent study include MCN1 [12,13,14] and MCN5. Stimulation of MCN5 increases the cycle frequency of both the fast and slow pyloric rhythms in the crab. Presumably, this is attributable to the fact that MCN5 excites several, and perhaps all, of the pyloric pacemaker neurons. In addition, MCN5 reduces the activity level in all non-pacemaker pyloric neurons by inhibiting them. Interestingly, the activity level in several of these neurons is enhanced above their prestimulation levels once MCN5 activity is terminated.
34. Elphick MR, Kemenes G, Staras K, O'Shea M: Behavioral role for nitric oxide in chemosensory activation of feeding in a mollusc. 7A/eurosc/1995, 15:7653-7664.
35. Quinlan E, Murphy A: Plasticity in the multifunctional buccal central pattern generator of Helisoma illuminated by the identification of phase 3 interneurons. J Neurophysiol 1996, 75:561-574. At a behavioral level, feeding in molluscs can consist of three phases. In the first, the buccal odontophore moves from a neutral to an extended position (protraction). The odontophore then returns to the neutral position (retraction) and, in some cases, hyper-retracts to deposit food in the esophagus. In some molluscs (e.g. Lymnaea), three sets of interneurons have been described that are apparently responsible for the generation of this tripartite behavior. Previous studies of Helisoma have identified S1 interneurons and a pair of glutamaterigc S2 interneurons. The source of the excitatory drive for the S3 phase of behavior had not, however, been identified. It had been suggested that post-inhibitory rebound at the motor neuron level might account for phase 3 burst generation. In this study, however, Quinlan and Murphy have shown that this is not the case. They have identified a bilaterally symmetrical pair of interneurons that depolarize phase 3 motor neurons.
36. Susswein AJ, Byrne JH: Identification and characterization of neurons initiating patterned neural activity in the buccal ganglia of Aplysia. J Neurose/ 1988, 8:2049-2061.
37. Hurwitz l, Goldstein RS, Susswein AJ: Compartmentalization of pattern-initiation and motor functions in the B31 and B32 neurons of the buccal ganglia of Aplysia californica. J Neurophysiol 1994, 71:1514-1527.
38. Hurwitz l, Neustadter D, Morton D, Chiel H, Susswein A: Activity patterns of the B31/B32 pattern initiators innervating the 12 muscle of the buccal mass during normal feeding movements in Aplysia californica. J Neurophysiol 1996, 75:1309-1326. Previous work has established that neurons B31/B32 have unusual membrane properties and can initiate patterned activity in the buccal ganglion of Aplysia californica. In this study, the authors show that in addition to being a part of the feeding, CPG B31/B32 are motor neurons and both cells innervate the 12 muscle. In addition, they took advantage of the motor function of B31 and B32 and recorded electromyograms from the 12 muscles of animals engaged in normal feeding behavior. Thus, they have determined that B31/B32 are active during the protraction phase of behavior.
39. Hurwitz I, Susswein A: B64, a newly identified central pattern generator element producing a phase switch from protraction to retraction in buccal motor programs of Aplysia californica. J Neurophysiol 1996, 75:1327-1344. As described above for rhythmic motor programs [38], B31 and B32 are also depolarized during protraction and clearly receive inhibitory synaptic input during retraction. Until recently, the source of the inhibitory input had not been described. In this study, the authors characterize a recently identified interneuron, B64, that has endogenous plateau properties and is capable of advancing or delaying buccal motor programs. Stimulation of a single B64 causes both bilateral inhibition of B31/B32 and other neurons active during protraction and bilateral excitation of neurons active during retraction. B64 appears, therefore, to be at least partially responsible for the phase shift from protraction to retraction in feeding motor programs.
40. Gamkrelidze G, Laurienti P, Blankenship J: Identification and characterization of cerebral ganglion neurons that induce swimming and modulate swim-related pedal ganglion neurons in Aplysia brasiliana. J Neurophysiol 1995, 74:1444-1462. Previous research has indicated that the Aplysia swimming CPG is in the pedal ganglion but that rhythmic swimming can be initiated by stimulation of the cerebral-pleura! connective (CPC) [46,47]. Thus, it has been hypothesized that the cerebral ganglion contains a swimming command system. In this study, which was designed to identify cerebral command elements, the authors identified and characterized a family of neurons that are capable of inducing or modulating a swimming motor program. Four classes of cerebral neurons are capable of initiating motor programs. These neurons are referred to as command neurons 1-4 (CN1-CN4). Some neurons are more effective than others. For example, tonic firing of the CN4 neurons only excites the swim motor program weakly, but CN4 neurons also excite CN1 and CN2 cells. All command neurons tested received strong input from mechanical stimulation of either parapodium.
41. Brodfuehrer P, Debski E, O'Gara B, Friesen W: Neuronal control of leech swimming. J Neurobiol 1995, 27:403-418.
42. O'Gara B, Friesen W: Termination of leech swimming activity by a previously identified swim trigger neuron. J Comp Physiol [A] 1995, 177:627-636. Neuron Tr2 is a previously described neuron that can trigger swim episodes in the leech [48]. In this role, however, Tr2 is not very effective -in most preparations tested, Tr2 does not initiate swimming. The authors of this paper re-examine the behavioral role of Tr2, and they show that Tr2 terminates swimming more reliably than it triggers it.
43. Brodfuehrer P, Burns A: Neuronal factors influencing the decision to swim in the medicinal leech. Neurobiol Learn Mem 1995, 63:192-199.
44. Norekian TP, Satterlie RA: Whole body withdrawal circuit and its involvement in the behavioral hierarchy of the mollusk Clione limacina. J Neurophysiol 1996, 75:529-537. The authors examine the relative priorities of three behaviors in Clione: feeding, withdrawal, and swimming. Specifically, a group of pleural neurons that control whole body withdrawal are described. These neurons, the PI-W cells, receive inhibitory inputs from cerebral neurons involved in feeding. The output of the PI-W is, in turn, inhibitory to swim motor neurons. Thus, withdrawal appears to dominate over slow swimming and feeding to dominate over withdrawal.
45. Norekian TP, Satterlie RA: Cerebral serotonergic neurons reciprocally modulate swim and withdrawal neural networks in the mollusk Clione limacina. J Neurophysiol 1996, 75:538-546. The authors identify a pair of serotonin-immunoreactive neurons (the CrSv neurons) in the cerebral ganglion that produce coordinated excitatory/inhibitory effects on neurons that control two incompatible behaviors: swimming and whole-body withdrawal. Specifically, stimulation of the Cr-Sv neurons inhibits the neurons that produce withdrawal (i.e. the PI-W neurons [44]) and excites swim motor neurons, the serotonergic heart excitor, and pedal serotonergic neurons that modulate swimming (i.e. the Pd-SW neurons [24-]).
46. Parsons DW, Pinsker HM: Swimming in Aplysia brasiliana: identification of parapodial opener-phase (POP) and closer phase (PCP) neurons. J Neurophysiol 1988, 59:717-739.
47. Von der Porten K, Parson DW, Rothman BS, Pinsker HM: Swimming in Aplysia brasiliana: analysis of behavior and neuronal pathways. Behav Neural Bio/1982, 36:1 -23.
48. Brodfuehrer PD, Fricson WO: Initiation of swimming in the leech subesophageal ganglion. I. Output connections of Tr1 and Tr2. J Comp Physiol [A] 1986, 159:489-502.