Neural analogue of long-term sensitization training produces long-term (24 and 48 h) facilitation of the sensory-to-motor neuron connection in Aplysia

1. An in vitro analogue of long-term sensitization training was used to gain insights into the mechanisms and time course of the memory for long-term sensitization in Aplysia. The analogue, consisting of four blocks of shocks, was delivered to peripheral nerves of the isolated pleural-pedal ganglia, which contain the sensory neurons and motor neurons that mediate the tail withdrawal reflex. 2. Long-term facilitation of the connections between the sensory neurons and motor neurons was produced by the conjoint stimulation of two peripheral nerves, P8 and P9. Long-term facilitation, however, was not observed after conjoint stimulation of three nerves, P7, P8, and P9. 3. The preparation was viable and stable (no changes in the amplitudes of excitatory postsynaptic potentials (EPSPs) and membrane properties in controls) for at least 48 h. Moreover, the long-term facilitation persisted for at least 48 h. 4. We observed no significant long-term changes in the resting membrane potentials of the sensory and motor neurons or in the input resistance of the motor neurons 24 and 48 h after the conjoint stimulation of nerves P8 and P9. Thus changes in these biophysical properties do not appear to contribute to the expression of long-term facilitation. 5. The finding that conjoint stimulation of three nerves, P7, P8, and P9, produced no long-term facilitation raised the possibility that stimulation of nerve P7 alone might produce long-term inhibition that opposes the facilitatory effects induced by conjoint stimulation of nerves P8 and P9. Stimulation of nerve P7 alone, however, had no long-term inhibitory effect on the EPSPs.(ABSTRACT TRUNCATED AT 250 WORDS)

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TGF-β1 in Aplysia: Role in Long-Term Changes in the Excitability of Sensory Neurons and Distribution of TβR-II-Like Immunoreactivity

Learning & Memory ◽

10.1101/lm.6.3.317 ◽

1999 ◽

Vol 6 (3) ◽

pp. 317-330

Author(s):

Jeannie Chin ◽

Annie Angers ◽

Leonard J. Cleary ◽

Arnold Eskin ◽

John H. Byrne

Keyword(s):

Synaptic Plasticity ◽

Sensory Neurons ◽

Motor Neurons ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Tissue Extracts ◽

The Central Nervous System ◽

Long Term Facilitation ◽

Tgf Β1

Exogenous recombinant human transforming growth factor β-1 (TGF-β1) induced long-term facilitation ofAplysia sensory-motor synapses. In addition, 5-HT-induced facilitation was blocked by application of a soluble fragment of the extracellular portion of the TGF-β1 type II receptor (TβR-II), which presumably acted by scavenging an endogenous TGF-β1-like molecule. Because TβR-II is essential for transmembrane signaling by TGF-β, we sought to determine whether Aplysia tissues contained TβR-II and specifically, whether neurons expressed the receptor. Western blot analysis of Aplysia tissue extracts demonstrated the presence of a TβR-II-immunoreactive protein in several tissue types. The expression and distribution of TβR-II-immunoreactive proteins in the central nervous system was examined by immunohistochemistry to elucidate sites that may be responsive to TGF-β1 and thus may play a role in synaptic plasticity. Sensory neurons in the ventral–caudal cluster of the pleural ganglion were immunoreactive for TβR-II, as well as many neurons in the pedal, abdominal, buccal, and cerebral ganglia. Sensory neurons cultured in isolation and cocultured sensory and motor neurons were also immunoreactive. TGF-β1 affected the biophysical properties of cultured sensory neurons, inducing an increase of excitability that persisted for at least 48 hr. Furthermore, exposure to TGF-β1 resulted in a reduction in the firing threshold of sensory neurons. These results provide further support for the hypothesis that TGF-β1 plays a role in long-term synaptic plasticity in Aplysia.

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Induction of long-term facilitation in Aplysia sensory neurons by local application of serotonin to remote synapses

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.90.23.11411 ◽

1993 ◽

Vol 90 (23) ◽

pp. 11411-11415 ◽

Cited By ~ 35

Author(s):

G A Clark ◽

E R Kandel

Keyword(s):

Gene Expression ◽

Sensory Neurons ◽

Cell Body ◽

Sensory Cells ◽

Target Cells ◽

Synaptic Terminals ◽

Dissociated Cell Culture ◽

Synaptic Changes ◽

Long Term Facilitation

Long-term synaptic facilitation at the connections of Aplysia sensory neurons onto their target cells involves alterations in gene expression. How then are the relevant cellular signals for the induction and expression of long-term synaptic changes conveyed between the nucleus and remote synaptic terminals? We have explored this question using a set of remote, peripheral terminals of siphon sensory cells, which are approximately 3 cm from the sensory cell body in the abdominal ganglion. We found that these remote synapses, like the proximal synapses previously studied in dissociated cell culture, can exhibit long-term facilitation 24 hr after cell-wide serotonin application. Furthermore, serotonin applications restricted to the remote synaptic terminals nevertheless produced long-term facilitation, indicating that signals generated in synaptic regions can trigger the long-term process, perhaps via retrograde signals to the nucleus to modify gene expression, followed by anterograde signals back to the terminal. Serotonin applications restricted to the cell body and proximal synapses of the sensory neuron also produced long-term facilitation at remote synapses, although to a lesser extent, suggesting that long-term facilitation is expressed cell-wide, but that superimposed on this cell-wide facilitation there appears to be a component that is synapse-specific.

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Synaptic Tagging during Synapse-Specific Long-Term Facilitation of Aplysia Sensory-Motor Neurons

Neurobiology of Learning and Memory ◽

10.1006/nlme.2002.4088 ◽

2002 ◽

Vol 78 (3) ◽

pp. 489-497 ◽

Cited By ~ 10

Author(s):

K Martin

Keyword(s):

Motor Neurons ◽

Sensory Motor ◽

Long Term Facilitation

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Connections between thoraco-coxal proprioceptive afferents and motor neurons in the locust

Journal of Experimental Biology ◽

10.1242/jeb.203.3.435 ◽

2000 ◽

Vol 203 (3) ◽

pp. 435-445

Author(s):

M. Wildman

Keyword(s):

Electrical Stimulation ◽

Sensory Neurons ◽

Motor Neurons ◽

Chordotonal Organ ◽

Synaptic Connections ◽

Afferent Neurons ◽

Postsynaptic Potentials ◽

The Common ◽

Proprioceptive Afferents ◽

Stimulation Of

The position of the coxal segment of the locust hind leg relative to the thorax is monitored by a variety of proprioceptors, including three chordotonal organs and a myochordotonal organ. The sensory neurons of two of these proprioceptors, the posterior joint chordotonal organ (pjCO) and the myochordotonal organ (MCO), have axons in the purely sensory metathoracic nerve 2C (N2C). The connections made by these afferents with metathoracic motor neurons innervating thoraco-coxal and wing muscles were investigated by electrical stimulation of N2C and by matching postsynaptic potentials in motor neurons with afferent spikes in N2C. Stretch applied to the anterior rotator muscle of the coxa (M121), with which the MCO is associated, evoked sensory spikes in N2C. Some of the MCO afferent neurons make direct excitatory chemical synaptic connections with motor neurons innervating the thoraco-coxal muscles M121, M126 and M125. Parallel polysynaptic pathways via unidentified interneurons also exist between MCO afferents and these motor neurons. Connections with the common inhibitor 1 neuron and motor neurons innervating the thoraco-coxal muscles M123/4 and wing muscles M113 and M127 are polysynaptic. Afferents of the pjCO also make polysynaptic connections with motor neurons innervating thoraco-coxal and wing muscles, but no evidence for monosynaptic pathways was found.

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Phrenic Long-Term Facilitation Requires PKC Activity within Phrenic Motor Neurons

Journal of Neuroscience ◽

10.1523/jneurosci.5086-14.2015 ◽

2015 ◽

Vol 35 (21) ◽

pp. 8107-8117 ◽

Cited By ~ 34

Author(s):

M. J. Devinney ◽

D. P. Fields ◽

A. G. Huxtable ◽

T. J. Peterson ◽

E. A. Dale ◽

...

Keyword(s):

Motor Neurons ◽

Long Term Facilitation

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Long-term facilitation alters transmitter releasing properties at the crayfish neuromuscular junction

Journal of Neurophysiology ◽

10.1152/jn.1986.55.3.484 ◽

1986 ◽

Vol 55 (3) ◽

pp. 484-498 ◽

Cited By ~ 40

Author(s):

J. M. Wojtowicz ◽

H. L. Atwood

Keyword(s):

Neuromuscular Junction ◽

Synaptic Transmission ◽

Time Course ◽

Muscle Fibers ◽

Low Frequencies ◽

Before And After ◽

Binomial Parameter ◽

Small Muscle ◽

Long Term Facilitation

Synaptic transmission at the neuromuscular junction of the excitatory axon supplying the crayfish opener muscle was examined before and after induction of long-term facilitation (LTF) by a 10-min period of stimulation at 20 Hz. Induction of LTF led to a period of enhanced synaptic transmission, which often persisted for many hours. The enhancement was entirely presynaptic in origin, since quantal unit size and time course were not altered, and quantal content of transmission (m) was increased. LTF was not associated with any persistent changes in action potential or presynaptic membrane potential recorded in the terminal region of the excitatory axon. The small muscle fibers of the walking-leg opener muscle were almost isopotential, and all quantal events could be recorded with an intracellular microelectrode. In addition, at low frequencies of stimulation, m was small. Thus it was possible to apply a binomial model of transmitter release to events recorded from individual muscle fibers and to calculate values for n (number of responding units involved in transmission) and p (probability of transmission for the population of responding units) before and after LTF. In the majority of preparations analyzed (6/10), amplitude histograms of evoked synaptic potentials could be described by a binomial distribution with a small n and moderately high p. LTF produced a significant increase in n, while p was slightly reduced. The results can be explained by a model in which the binomial parameter n represents the number of active synapses and parameter p the mean probability of release at a synapse. Provided that a pool of initially inactive synapses exists, one can postulate that LTF involves recruitment of synapses to the active state.

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Mechanisms Involved in Persistent Facilitation of Neuromuscular Synapses in Aplysia

Journal of Neurophysiology ◽

10.1152/jn.00142.2001 ◽

2002 ◽

Vol 87 (4) ◽

pp. 2018-2030 ◽

Cited By ~ 5

Author(s):

Lyle E. Fox ◽

Philip E. Lloyd

Keyword(s):

Motor Neurons ◽

Neuromuscular Synapses ◽

Camp Pathway ◽

Kinase C ◽

Withdrawal Reflexes ◽

Central Synapses ◽

Long Term Facilitation ◽

Camp Levels ◽

New Protein

Synaptic plasticity can last from a fraction of a second to weeks depending on how it was induced. The mechanisms that underlie short-, intermediate-, and long-term plasticity have been intensively studied at central synapses of both vertebrates and invertebrates; however, peripheral plasticity has not received as much attention. In this study, we investigated the mechanisms that contribute to a persistent form of plasticity at neuromuscular synapses in buccal muscle I3a of Aplysia.These synapses are reversibly facilitated by the small cardioactive peptide (SCP), a peptide cotransmitter that is intrinsic to the motor neurons, and persistently facilitated by serotonin (5HT) released from modulatory neurons that are extrinsic to the motor circuit. Many of the short-term effects of 5HT and SCP are mediated by the cAMP pathway, but little is known about the mechanisms that underlie persistent modulation. We were able to eliminate several possible mechanisms. One of these was the possibility that the apparent reversal of SCP's effects was due to desensitization of the SCP receptor. Superfusion for longer periods or with higher concentrations of SCP indicate that the SCP receptors do not desensitize. We also determined that new protein synthesis is not required for the persistent facilitation of EJPs. Another possibility was that 5HT was taken up and slowly re-released. Our results suggest that this mechanism is also unlikely. Activation of the cAMP pathway does not appear to mediate persistent effects; however, 5HT as well as SCP does cause persistent increases in cAMP levels that can prime I3a synapses and increase the effectiveness of activators of the cAMP pathway. Instead, the persistent effects of 5HT are mimicked by phorbol, suggesting that protein kinase C or an Aplysia homologue of unc13 may mediate these effects. These results, in combination with results from experiments on the sensory neurons that contribute to withdrawal reflexes in Aplysia, suggest that the mechanisms for intermediate- and long-term facilitation may reside in all of the synapses involved in the sensory to motor response reflex.

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Acute intermittent optogenetic stimulation of nucleus tractus solitarius neurons induces sympathetic long-term facilitation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00381.2014 ◽

2015 ◽

Vol 308 (4) ◽

pp. R266-R275 ◽

Cited By ~ 15

Author(s):

Kenta Yamamoto ◽

Peter Lalley ◽

Steve Mifflin

Keyword(s):

Nucleus Tractus Solitarius ◽

Respiratory Drive ◽

Nerve Activity ◽

Mechanically Ventilated ◽

Afferent Activation ◽

Power Spectral ◽

Long Term Facilitation ◽

Renal Sympathetic ◽

Stimulation Of

Acute intermittent hypoxia (AIH) induces sympathetic and phrenic long-term facilitation (LTF), defined as a sustained increase in nerve discharge. We investigated the effects of AIH and acute intermittent optogenetic (AIO) stimulation of neurons labeled with AAV-CaMKIIa, hChR2(H134R), and mCherry in the nucleus of the solitary tract (NTS) of anesthetized, vagotomized, and mechanically ventilated rats. We measured renal sympathetic nerve activity (RSNA), phrenic nerve activity (PNA), power spectral density, and coherence, and we made cross-correlation measurements to determine how AIO stimulation and AIH affected synchronization between PNA and RSNA. Sixty minutes after AIH produced by ventilation with 10% oxygen in balanced nitrogen, RSNA and PNA amplitude increased by 80% and by 130%, respectively ( P < 0.01). Sixty minutes after AIO stimulation, RSNA and PNA amplitude increased by 60% and 100%, respectively, ( P < 0.01). These results suggest that acute intermittent stimulation of NTS neurons can induce renal sympathetic and phrenic LTF in the absence of hypoxia or chemoreceptor afferent activation. We also found that while acute intermittent optogenetic and hypoxic stimulations increased respiration-related RSNA modulation ( P < 0.01), they did not increase synchronization between central respiratory drive and RSNA. We conclude that mechanisms that induce LTF originate within the caudal NTS and extend to other interconnecting neuronal elements of the central nervous cardiorespiratory network.

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