Differential effects of tetanus toxin on inhibitory and excitatory synaptic transmission in mammalian spinal cord neurons in culture: a presynaptic locus of action for tetanus toxin

Tetanus toxin reduces monosynaptic inhibitory and excitatory synaptic transmission in mouse spinal cord neurons in culture. Inhibitory transmission is preferentially reduced by the toxin; however, excitatory transmission is also ultimately reduced and blocked by the concentrations of toxin used in these studies. Recordings from monosynaptically connected cell pairs revealed a marked diminution in amplitude of evoked monosynaptic inhibitory postsynaptic potentials coincident with the onset of convulsant action at a time when evoked monosynaptic EPSPs were relatively unaffected. Increased polysynaptic excitation occurred as a result of diminished inhibition. This supports the reduction of inhibition as an important mechanism in the convulsant action of tetanus toxin. Quantal analysis of the late effects of tetanus toxin on the monosynaptic excitatory postsynaptic potential revealed a reduction in quantal number with no reduction in quantal size, thus demonstrating a presynaptic locus of action for the toxin on spinal neurons.

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Ammonium decreases excitatory synaptic transmission in cat spinal cord in vivo

Journal of Neurophysiology ◽

10.1152/jn.1989.62.6.1461 ◽

1989 ◽

Vol 62 (6) ◽

pp. 1461-1473 ◽

Cited By ~ 15

Author(s):

W. Raabe

Keyword(s):

Spinal Cord ◽

Synaptic Transmission ◽

Action Potentials ◽

Conduction Block ◽

Excitatory Synaptic Transmission ◽

Excitatory Postsynaptic Potential ◽

Presynaptic Terminals ◽

Ia Afferent ◽

Afferent Fibers ◽

Low Threshold

1. Glutamine is thought to be a precursor of the pool of glutamate that is used as synaptic transmitter. NH4+ inhibits glutaminase, the enzyme presumed to cleave glutamine into glutamate in synaptic terminals. Therefore a decrease by NH4+ of excitatory synaptic transmission in hippocampus was suggested to be due to the inability to utilize glutamine as a precursor for glutamate and subsequent transmitter depletion. This study reexamines the effects of NH4+ on excitatory synaptic transmission. 2. The effects of NH4+ on excitatory synaptic transmission from low-threshold afferent fibers, presumably Ia-afferent fibers, to motoneurons was investigated in the spinal cord of anesthetized cats in vivo. 3. Action potentials of low-threshold afferent fibers were recorded at the entry of the dorsal roots into the spinal cord. An extracellular electrode within a motoneuron nucleus recorded the action potential of low-threshold afferent fibers and the extracellular monosynaptic excitatory postsynaptic potential, i.e., the focal synaptic potential (FSP). This extracellular electrode also recorded the antidromic field potential (AFP) in response to ventral root stimulation. Electrodes on the ventral roots recorded the monosynaptic reflex (MSR) and the monosynaptic excitatory postsynaptic potential in motoneurons electrotonically conducted into the ventral roots (VR-EPSP). 4. Intravenous infusion of ammonium acetate (AA) reversibly decreased MSR, VR-EPSP, and FSP, i.e., decreased excitatory synaptic transmission. 5. The decrease of VR-EPSP and FSP was accompanied initially by a decrease of conduction and, eventually, a conduction block in presynaptic terminals of low-threshold afferent fibers. 6. The decreases of VR-EPSP and FSP were also accompanied by the transient appearance of a reflex discharge, triggered by VR-EPSPs of decreased amplitude, and changes of the AFP indicating increased invasion of motoneuron somata by antidromic action potentials. 7. It is suggested that NH4+ depolarizes intraspinal Ia-afferent fibers and motoneurons. This depolarization initially decreases and then blocks conduction of action potentials into the presynaptic terminals of Ia-afferent fibers. The conduction block prevents the release of excitatory transmitter and decreases excitatory synaptic transmission. 8. The suggested depolarizing action of NH4+ may be due to K+-like ionic properties of NH4+ and/or an inhibition of K+-uptake into astrocytes. 9. The conduction block in presynaptic terminals of low-threshold afferent fibers can fully explain the decrease of excitatory synaptic transmission by NH4+. Because of the conduction block in presynaptic terminals, this study does not permit a conclusion as to an inhibition by NH4+ fo the utilization of glutamine as a precursor for glutamate used as synaptic transmitter.

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Quantal synaptic transmission in phrenic motor nucleus

Journal of Neurophysiology ◽

10.1152/jn.1992.68.4.1468 ◽

1992 ◽

Vol 68 (4) ◽

pp. 1468-1471 ◽

Cited By ~ 19

Author(s):

G. Liu ◽

J. L. Feldman

Keyword(s):

Spinal Cord ◽

Synaptic Transmission ◽

Amplitude Distribution ◽

Excitatory Synaptic Transmission ◽

Neonatal Rat ◽

Respiratory Neurons ◽

Motor Nucleus ◽

Patch Clamp Recording ◽

Epsc Amplitude ◽

Quantal Size

1. The quantal nature of excitatory synaptic transmission was studied in respiratory interneurons and phrenic motoneurons of intact neonatal rat brain stem-spinal cord preparations in vitro. Synaptic currents were recorded with whole-cell patch-clamp recording techniques. 2. Because the most important factor for quantal detection is the ratio of quantal size to quantal standard deviation, factors that influence this ratio were evaluated so that experimental techniques that enhance this ratio could be defined. 3. Under favorable conditions, we directly observed quantal amplitude fluctuations in spontaneous excitatory postsynaptic currents (EPSCs) in spinal cord respiratory neurons. The quantal conductance size was 55-100 pS. With fast decay of these EPSCs, the charge reaching the soma for a single quantum is only approximately 15 fC (Vh = -80 mV). 4. We also studied miniature EPSC amplitude distributions. These were skewed, as previously reported; however, distinct quantal intervals were observed. Furthermore, in three cells tested, the quantal size in the miniature EPSC amplitude distribution was similar to the quantal size in the spontaneous EPSC amplitude distribution. 5. We conclude that excitatory synaptic transmission in the mammalian spinal cord is quantal and that the apparent skewness of miniature EPSC distributions results from summation of events with multiple quantal peak amplitudes.

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Development of Excitatory Circuitry in the Hippocampus

Journal of Neurophysiology ◽

10.1152/jn.1998.79.4.2013 ◽

1998 ◽

Vol 79 (4) ◽

pp. 2013-2024 ◽

Cited By ~ 166

Author(s):

Albert Y. Hsia ◽

Robert C. Malenka ◽

Roger A. Nicoll

Keyword(s):

Synaptic Transmission ◽

Action Potentials ◽

Pyramidal Cells ◽

Excitatory Synaptic Transmission ◽

Developmental Strategy ◽

Excitatory Postsynaptic Currents ◽

Postsynaptic Currents ◽

Quantal Size ◽

Physiological Approach ◽

Local Circuitry

Hsia, Albert Y., Robert C. Malenka, and Roger A. Nicoll. Development of excitatory circuitry in the hippocampus. J. Neurophysiol. 79: 2013–2024, 1998. Assessing the development of local circuitry in the hippocampus has relied primarily on anatomic studies. Here we take a physiological approach, to directly evaluate the means by which the mature state of connectivity between CA3 and CA1 hippocampal pyramidal cells is established. Using a technique of comparing miniature excitatory postsynaptic currents (mEPSCs) to EPSCs in response to spontaneously occurring action potentials in CA3 cells, we found that from neonatal to adult ages, functional synapses are created and serve to increase the degree of connectivity between CA3-CA1 cell pairs. Neither the probability of release nor mean quantal size was found to change significantly with age. However, the variability of quantal events decreases substantially as synapses mature. Thus in the hippocampus the developmental strategy for enhancing excitatory synaptic transmission does not appear to involve an increase in the efficacy at individual synapses, but rather an increase in the connectivity between cell pairs.

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Features of laminar and somatotopic organization of lumbar spinal cord units receiving cutaneous inputs from hindlimb receptive fields

Journal of Neurophysiology ◽

10.1152/jn.1984.52.3.449 ◽

1984 ◽

Vol 52 (3) ◽

pp. 449-458 ◽

Cited By ~ 40

Author(s):

A. R. Light ◽

R. G. Durkovic

Keyword(s):

Spinal Cord ◽

Receptive Field ◽

Receptive Fields ◽

Lumbar Spinal Cord ◽

Spinal Neurons ◽

Spinal Cord Neurons ◽

Somatotopic Organization ◽

Single Unit Recordings ◽

Lumbar Spinal ◽

Rectangular Columns

Single-unit recordings from 312 units of lamina I-VII of the lumbar spinal cord of unanesthetized, decerebrate, T8 spinal cats were used to determine the somatotopic and laminar organization of spinal neurons responding to cutaneous stimulation of the hindlimb. Properties of cells confined to different Rexed laminae (I-VII) were shown to differ in several respects, including responses to variations in stimulus intensity, receptive-field areas, spontaneous frequencies, and central delays. Spinal cord neurons with similarly localized cutaneous receptive fields were found to be organized in sagittally oriented rectangular columns. These columns were 7 to at least 20 mm long (rostral-caudal axis), 0.5-1.0 mm wide, and could encompass laminae I-VII in depth. Touch, pressure, and pinch were effective excitatory inputs into each column subserving a given receptive-field location. A map of the somatotopic organization of units in the horizontal plane is presented, which in general confirms previous reports and in particular deals with the organization of units with receptive fields on the plantar cushion and individual toes.

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Modulation of excitatory synaptic transmission by nociceptin in superficial dorsal horn neurones of the neonatal rat spinal cord

British Journal of Pharmacology ◽

10.1038/sj.bjp.0701149 ◽

1997 ◽

Vol 121 (3) ◽

pp. 425-432 ◽

Cited By ~ 97

Author(s):

Jörg T. Liebel ◽

Dieter Swandulla ◽

Hanns Ulrich Zeilhofer

Keyword(s):

Spinal Cord ◽

Synaptic Transmission ◽

Dorsal Horn ◽

Excitatory Synaptic Transmission ◽

Neonatal Rat ◽

Superficial Dorsal Horn ◽

Rat Spinal Cord ◽

Dorsal Horn Neurones

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Responses of T2-4 spinal cord neurons to irritation of the lower airways in the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.3.r1147 ◽

1997 ◽

Vol 273 (3) ◽

pp. R1147-R1157 ◽

Cited By ~ 7

Author(s):

T. Hummel ◽

J. N. Sengupta ◽

S. T. Meller ◽

G. F. Gebhart

Keyword(s):

Spinal Cord ◽

Afferent Input ◽

Sprague Dawley ◽

Spinal Neurons ◽

Thoracic Spinal Cord ◽

Spinal Cord Neurons ◽

Thoracic Spinal ◽

Balloon Distension ◽

Sprague Dawley Rats ◽

Lower Airways

The aim of the study was to investigate the information processing in the thoracic spinal cord (T2-4) after chemical irritation of the lower airways. Experiments were performed in pentobarbital sodium-anesthetized and pancuronium-paralyzed male Sprague-Dawley rats. Balloon distension of the esophagus was used as the search stimulus. Ammonia and smoke were applied by means of a tracheal cannula; they produced excitatory, inhibitory, and biphasic responses in a concentration-related manner (ammonia 39/39; smoke 23/ 39). Inhaled irritant-responsive neurons exhibited a number of similarities that have been described for neurons responding to stimulation of other thoracic viscera. These similarities relate to the distribution of neurons in the deeper laminae of the thoracic spinal cord, the relatively small number of neurons receiving input from the lower airways, the extensive convergent input from the skin and other thoracic viscera, and the pattern of responses. In addition, both stimulus-induced responses and spontaneous activity are subject to modulation from supraspinal sites. On the basis of responses to inhaled irritants after either spinal cord or vagus nerve block/transection, these T2-4 spinal neurons are likely to receive spinal afferent input that is modulated by vagal-brain stem input.

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Effects of NH4+ on reflexes in cat spinal cord

Journal of Neurophysiology ◽

10.1152/jn.1990.64.2.565 ◽

1990 ◽

Vol 64 (2) ◽

pp. 565-574 ◽

Cited By ~ 13

Author(s):

W. Raabe

Keyword(s):

Spinal Cord ◽

Synaptic Transmission ◽

Nerve Stimulation ◽

Action Potentials ◽

Presynaptic Inhibition ◽

Excitatory Synaptic Transmission ◽

P Wave ◽

Postsynaptic Inhibition ◽

Presynaptic Terminals ◽

Muscle Nerve

1. In deeply barbiturate-anesthetized animals. NH4+ decreases spinal excitatory synaptic transmission by neuronal depolarization and subsequent block of conduction of action potentials into presynaptic terminals of low-threshold (presumably Ia-) afferents. Because barbiturates by themselves depress excitatory synaptic transmission and may have modified the effects of NH4+, this study examines the effect of NH4+ on excitatory synaptic transmission in the unanesthetized animal. 2. The effects of NH4+ on monosynaptic and polysynaptic excitatory reflexes as well as di- and polysynaptic inhibition were investigated in the spinal cord of the decerebrate and unanesthetized cat in vivo. 3. The monosynaptic excitatory reflex (MSR) elicited by muscle nerve stimulation and polysynaptic excitatory reflexes elicited by muscle (MSR-PSR) or cutaneous nerve stimulation (Cut-PSR) were recorded from the ventral roots L7 or S1. The P-wave was recorded from the cord dorsum. Di- and polysynaptic inhibition was elicited by muscle nerve stimulation and measured as decrease of the MSR. 4. Intravenous infusion of ammonium acetate (AA) decreased MSR and the monosynaptic motoneuron pool excitatory postsynaptic potential (EPSP) recorded from the ventral root (VR-EPSP). Decrease of MSR and VR-EPSP was accompanied by an increase of the intraspinal conduction time in presynaptic terminals. The maximal decrease of the MSR was preceded by a period of transient increase of the MSR and reflex discharges from previously subthreshold VR-EPSPs. 5. The effects of NH4+ on MSR and VR-EPSP are consistent with those in barbiturate-anesthetized animals and suggest that NH4+ also decreases monosynaptic excitation in unanesthetized animals by depolarization and subsequent conduction block for action potentials in presynaptic terminals. 6. Decrease of the MSR was accompanied by a decrease of the P-wave, indicating that NH4+ simultaneously decreases mono- and oligosynaptic excitatory synaptic transmission as well as presynaptic inhibition. 7. Decrease of the MSR was accompanied by increases of MSR-PSR and Cut-PSR and decreases of di- and polysynaptic postsynaptic inhibition. 8. The neuronal circuits underlying MSR-PSR and Cut-PSR include presynaptic inhibition of group I and II afferents as well as postsynaptic inhibition of motoneurons. It is suggested that increases of MSR-PSR and Cut-PSR are contributed to by decreases of pre- and postsynaptic inhibition and neuronal depolarization by NH4+. These effects increase afferent input to motoneurons, permit uncontrolled discharge of motoneurons, and initiate reflex discharges by previously subthreshold excitatory postsynaptic potentials.

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