A Simple Technique for Monitoring the Synaptic Actions of Pharmacological Agents

1973 ◽  
Vol 59 (3) ◽  
pp. 725-738
Author(s):  
J. J. CALLEC ◽  
D. B. SATTELLE

1. A simple electrophysiological method for the pharmacological investigation of synaptic transmission in insects is described. 2. By means of this technique synaptic potentials and ganglionic polarization can be recorded from the sixth abdominal ganglion of Periplaneta americana L. for long periods. 3. In the absence of stimulation, spontaneous excitatory (EPSP) and inhibitory (IPSP) postsynaptic potentials can be recorded. The mechanical stimulation of cercal receptors demonstrates the summation of EPSPs leading to spike generation. 4. Electrical stimulation of the cercal nerves (X, XI) enables the recording of a monosynaptic EPSP (XI) and a bisynaptic IPSP (X). 5. The action of acetylcholine on synaptic transmission, including a dose-response curve, is described. 6. The potential of this technique as a tool in pharmacological research is discussed.

1976 ◽  
Vol 64 (1) ◽  
pp. 13-23
Author(s):  
D. B. Sattelle ◽  
A. S. McClay ◽  
R. J. Dowson ◽  
J. J. Callec

1. Methods for presenting dose-response data for the ganglionic actions of cholinergic agonists (e.g. carbamylcholine) are compared, using the mannitol-gap technique for electrophysiological recording of synaptic events at the cercal nerve, giant fibre synapse of the sixth abdominal ganglion of the cockroach Periplaneta americana. 2. At concentrations around 10(−5)M, carbamylcholine has no effect on ganglionic polarization but potentiates the monosynaptic EPSP. At 10(−4)M and higher concentrations, ganglionic depolarization is accompanied by a reduction of EPSP. 3. Pretreatment with eserine (10(−6) M) considerably shifts the dose-response curve for acetylcholine so that synaptic transmission is consistently sensitive to 10(−6) M acetylcholine.


1997 ◽  
Vol 78 (3) ◽  
pp. 1363-1372 ◽  
Author(s):  
H. Straka ◽  
S. Biesdorf ◽  
N. Dieringer

Straka, H., S. Biesdorf, and N. Dieringer. Canal-specific excitation and inhibition of frog second-order vestibular neurons. J. Neurophysiol. 78: 1363–1372, 1997. Second-order vestibular neurons (2°VNs) were identified in the in vitro frog brain by their monosynaptic excitation following electrical stimulation of the ipsilateral VIIIth nerve. Ipsilateral disynaptic inhibitory postsynaptic potentials were revealed by bath application of the glycine antagonist strychnine or of the γ-aminobutyric acid-A (GABAA) antagonist bicuculline. Ipsilateral disynaptic excitatory postsynaptic potentials (EPSPs) were analyzed as well. The functional organization of convergent monosynaptic and disynaptic excitatory and inhibitory inputs onto 2°VNs was studied by separate electrical stimulation of individual semicircular canal nerves on the ipsilateral side. Most 2°VNs (88%) received a monosynaptic EPSP exclusively from one of the three semicircular canal nerves; fewer 2°VNs (10%) were monosynaptically excited from two semicircular canal nerves; and even fewer 2°VNs (2%) were monosynaptically excited from each of the three semicircular canal nerves. Disynaptic EPSPs were present in the majority of 2°VNs (68%) and originated from the same (homonymous) semicircular canal nerve that activated a monosynaptic EPSP in a given neuron (22%), from one or both of the other two (heteronymous) canal nerves (18%), or from all three canal nerves (28%). Homonymous activation of disynaptic EPSPs prevailed (74%) among those 2°VNs that exhibited disynaptic EPSPs. Disynaptic inhibitory postsynaptic potentials (IPSPs) were mediated in 90% of the tested 2°VNs by glycine, in 76% by GABA, and in 62% by GABA as well as by glycine. These IPSPs were activated almost exclusively from the same semicircular canal nerve that evoked the monosynaptic EPSP in a given 2°VN. Our results demonstrate a canal-specific, modular organization of vestibular nerve afferent fiber inputs onto 2°VNs that consists of a monosynaptic excitation from one semicircular canal nerve followed by disynaptic excitatory and inhibitory inputs originating from the homonymous canal nerve. Excitatory and inhibitory second-order (2°) vestibular interneurons are envisaged to form side loops that mediate spatially similar but dynamically different signals to 2° vestibular projection neurons. These feedforward side loops are suited to adjust the dynamic response properties of 2° vestibular projection neurons by facilitating or disfacilitating phasic and tonic input components.


1981 ◽  
Vol 55 (3) ◽  
pp. 420-430 ◽  
Author(s):  
Ronald F. Young ◽  
Terrence D. Oleson ◽  
Kent M. Perryman

✓ Trigeminal tractotomy near the level of the obex was carried out in 10 macaque monkeys. Behavioral responses were evaluated by a quantitative paradigm measuring lever-press responses to electrical stimulation of the dental pulp or facial skin, and by assessing facial response to cutaneous pin-scratch before and after the tractotomy. Two pharmacological agents, strychnine and L-dopa, were administered and their effect on behavioral responses to these stimuli was studied. Tractotomy did not produce dental analgesia. Thresholds for escape from cutaneous electrical stimulation of facial skin, however, were elevated, consistent with marked hypalgesia to pin-scratch. The adversive responses to pin-scratch were absent in peripheral portions of the face, but near the midline and inside the oral cavity they were usually decreased or normal. Pharmacological agents caused a reduction in escape thresholds to cutaneous electrical stimulation and a shrinkage or abolition of the zone of analgesia to pinscratch. The results imply that trigeminal nucleus caudalis, which undergoes deafferentation by tractotomy, may not be essential for processing of nociceptive information from the teeth, oral cavity, and midline facial zones. This finding is contrary to long-held hypotheses concerning facial pain mechanisms. The ability of strychnine and L-dopa to alter nociceptive escape thresholds is consistent with the idea, suggested by Denny-Brown, that facial nociception depends on central summation in the entire spinal trigeminal nucleus from overlapping afferent inputs contained in the trigeminal nerve, other cranial nerves, and the upper cervical nerve roots.


1982 ◽  
Vol 96 (1) ◽  
pp. 131-141
Author(s):  
G. A. BRADFISCH ◽  
C. D. DREWES ◽  
J. A. MUTCHMOR

1. The effects of cooling were studied in relation to (a) the impairment of locomotion (i.e. chill-coma) and (b) the functioning of various components of the monosynaptic trochanteral hair plate reflex in the cockroach, Peri-planeta americana. 2. The mean temperature for onset of chill-coma was 10.5 °C. At this temperature animals were unable to right themselves and visible tremors of the legs and body occurred. 3. Extracellular recordings from metathoracic nerve 5 indicated that cooling from 24 to 15 °C caused a decrease in the background spiking rate of motor neurone Ds. However, cooling from 12 to 9 °C caused a marked increase in the spiking frequency of both Ds and other unidentified neurones. This increase in spiking activity is the probable basis of leg and body tremors that occur during chill-coma. 4. Monosynaptic coupling between hair plate afferent spikes and Ds spikes (following electrical stimulation of the hair plate) was markedly affected by cooling. At 25 °C, hair plate afferent and Ds spikes were always tightly coupled to one another, whereas at 10 °C coupling was very weak. Several lines of evidence suggest that this loss of coupling was the result of failure of central synaptic transmission. The reduced effectiveness of central synaptic transmission during cooling may be a critical factor in the impairment of locomotor ability associated with chill-coma.


1998 ◽  
Vol 80 (2) ◽  
pp. 638-646 ◽  
Author(s):  
Y. Shoji ◽  
E. Tanaka ◽  
S. Yamamoto ◽  
H. Maeda ◽  
H. Higashi

Shoji, Y., E. Tanaka, S. Yamamoto, H. Maeda, and H. Higashi. Mechanisms underlying the enhancement of excitatory synaptic transmission in basolateral amygdala neurons of the kindling rat. J. Neurophysiol. 80: 638–646, 1998. To elucidate the mechanism underlying epileptiform discharges in kindled rats, synaptic responses in kindled basolateral amygdala neurons in vitro were compared with those from control rats by using intracellular and whole cell patch-clamp recordings. In kindled neurons, electrical stimulation of the stria terminalis induced epileptiform discharges. The resting potential, apparent input resistance, current-voltage relationship of the membrane, and the threshold, amplitude, and duration of action potentials in kindled neurons were not different from those in control neurons. The electrical stimulation of stria terminalis elicited excitatory postsynaptic potentials (EPSPs) and dl-2-amino-5-phosphonopentanoic acid (AP5)-sensitive and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic currents (EPSCs). The amplitude of evoked EPSPs and of evoked AP5-sensitive and CNQX-sensitive EPSCs were enhanced markedly, whereas fast and slow inhibitory postsynaptic potentials (IPSPs) induced by electrical stimulation of lateral amygdaloid nucleus were not significantly different. The rise time and the decay time constant of the evoked CNQX-sensitive EPSCs were shortened, whereas the rise time of the evoked AP5-sensitive EPSCs was shortened, but the decay time constants were not significantly different. In both tetrodotoxin (TTX)-containing medium and low Ca2+ and TTX-containing medium, the frequency and amplitude of spontaneous EPSCs were increased in kindled neurons. These increases are presumably due to nearly synchronous multiquantal events resulted from the increased probability of Glu release at the nerve terminals. The rise time of evoked CNQX- and AP5-sensitive EPSCs and the decay time constant of evoked CNQX-sensitive EPSCs were shortened, suggesting that excitatory synapses at the proximal dendrite and/or the soma in kindled neurons may contribute more effectively to generate evoked EPSCs than those at distal dendrites. In conclusion, the increases in the amplitudes of spontaneous and evoked EPSCs and in the frequency of spontaneous EPSCs may contribute to the epileptiform discharges in kindled neurons.


1976 ◽  
Vol 65 (3) ◽  
pp. 517-527
Author(s):  
B. Hue ◽  
M. Pelhate ◽  
J. J. Callec ◽  
J. Chanelet

1. Study was made of the action of 4-aminopyridine (5 X 10(−5) M) on synaptic transmission in the last abdominal ganglion of Periplaneta americana. The ‘oil-gap’ technique was used to record postsynaptic events in a single giant axon. 2. 4-AP quickly increased the ‘background’ of postsynaptic activity, which consisted of ‘spontaneous’ unitary EPSPs and IPSPs. Postsynaptic spikes were also propagated. 3. Both evoked EPSPs (stimulation of cercal nerve XI) and evoked IPSPs (stimulation of cercal nerve X) were greatly increased in amplitude although their duration (half-time) was unaltered. 4. 4-AP triggered presynaptic action potentials in the cercal nerves (recorded with external electrodes). These ‘antidromic’ potentials appeared singly or sometimes repetitively, especially after electrical stimulation of the cercal nerves. They were often in monosynaptic correlation with unitary EPSPs. 5. Neither the resting potential nor the postsynaptic membrane resistance was modified. 6. There were no changes in the equilibrium potentials of the ions involved in postsynaptic events. 7. The results may be essentially explained by an increase in transmitter release after 4-AP treatment, which may be partly the result of a rise in presynaptic terminal excitability, and partly the result of a lengthening of the presynaptic action potentials.


1970 ◽  
Vol 52 (3) ◽  
pp. 593-601
Author(s):  
K. J. FRIEDMAN ◽  
A. D. CARLSON

1. The study of insect curarization in the cockroach, Periplaneta americana, has been continued. The application of curare solution (0.032 M dTC) to the nerve cord produced blockage of action-potential conduction in the giant fibres lying within the nerve cord. 2. The application of curare solution to the cerci prevented the recording of action potentials from the cercal nerves of the organism. Application of dTC to the cercal nerve-A6 region of the cockroach prevented giant fibres from responding to electrical stimulation of the cercal nerves. These results are interpreted as indicating that curare blocks the conduction of action potentials in the cercal nerve. 3. It is proposed that curare can induce blockage of conduction in sensory, motor and central nervous system fibres. It is further proposed that this blockage of conduction is the mechanism of insect curarization. 4. The results of previous reports concerned with insect curarization are re-interpreted in view of the proposal. Several of the conflicts in these reports are resolved by the proposal that blockage of conduction is the mechanism of insect curarization.


1980 ◽  
Vol 43 (2) ◽  
pp. 332-342 ◽  
Author(s):  
E. Carstens ◽  
D. Klumpp ◽  
M. Zimmermann

1. The inhibitory effects of electrical stimulation in midbrain periaqueductal gray (PAG) and lateral reticular formation (LRF) on spinal dorsal horn neuronal responses to noxious skin heating were investigated in cats anesthetized with Nembutal and N2O. 2. Thirty-one dorsal horn units driven by electrical stimulation of the posterior tibial and/or superficial peroneal nerves at A- and C-fiber strength responded to noxious radiant heating (e.g., 50 degrees C) of the skin of the hindpaw. All units tested were inhibited by electrical stimulation (100-Hz trains, 3/s) of both PAG and LRF. 3. Systematic tracking with the stimulating electrode revealed that descending inhibition is generated at sites throughout the mediolateral extent of the midbrain. Particularly effective sites were in LRF and PAG. 4. More powerful descending inhibition was generated from LRF than from PAG sites, based on quantitative comparison in the same unit of a) degree of inhibition of spinal unit heat-evoked discharges by PAG and LRF stimulation at the same current intensity, b) current threshold for inhibition by PAG and LRF stimulation, and c) slope of curves plotting degree of inhibition in relation to intensity of PAG and LRF stimulation. 5. Dorsal horn neurons show a linear relationship between response magnitude and temperature of skin heating during a series of heat stimuli (42-50 degrees C) applied at 3-min intervals. When the series is repeated during PAG stimulation, the slope of the linear temperature-response curve is reduced without a change in the response threshold. In contrast, repetition of the heating series during LRF stimulation produced a parallel rightward shift in the linear temperature-response curve, with commensurate increase in response threshold. 6. The results indicate that functionally separate descending inhibitory systems are activated by stimulation of PAG and LRF. Possible inhibitory mechanisms and the functional significance of descending inhibition from PAG and LRF are discussed.


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