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PubMed1995

Temporal constraints in associative synaptic plasticity in hippocampus and neocortex.

We present comparative experimental evidence for the induction of synaptic potentiation and depression in organotypic cultures of hippocampus and in visual cortex in vitro and in vivo. The effects of associative pairings on the efficacy of synaptic transmission are analyzed as a function of the temporal delay between presynaptic activity and post-synaptic changes imposed in membrane potential. Synchronous association at a low temporal frequency (< 0.5 Hz) between presynaptic input and postsynaptic depolarization resulted in homosynaptic potentiation of functionally identified postsynaptic potentials in the three types of preparation. Synchronous pairing of afferent activity with hyperpolarization of the postsynaptic cell resulted in homosynaptic depression in visual cortex in vivo and in vitro. An associative form of depression was induced in hippocampus when the test input was followed repeatedly with a fixed-delay postsynaptic depolarization imposed either by intracellular current injection or synaptically. The latter process might play a significant role in heterosynaptic plasticity in visual cortex in vivo and in vitro, if it is assumed that associative depression still operates in visual cortex a few seconds after the initial surge of calcium in the postsynaptic cell. We conclude that the precise timing between presynaptic activity and polarization changes in postsynaptic membrane potential up- and down-regulates the efficacy of active pathways.

Adult↗
PubMed1983

Effects of somatostatin on mammalian cortical neurons in culture: physiological actions and unusual dose response characteristics.

Somatostatin was applied to rat cortical neurons grown in dispersed cell culture while electrophysiological effects were monitored with intracellular recordings. The effects of somatostatin were predominantly excitatory, but they varied and were dose dependent. Somatostatin at concentrations between 100 pM and 1 microM depolarized 30 of 87 neurons, often with a concomitant increase in spontaneous action potentials and a small increase in membrane input resistance. Somatostatin also increased the frequency of synaptic activity coming into the recorded neuron in 45 of 78 recordings, an effect which was seen even in the absence of direct effects. In six of nine neurons, somatostatin decreased the amplitude of large ongoing inhibitory synaptic potentials, concomitant with an increase in membrane input resistance. Somatostatin occasionally caused inhibition of neuronal activity, an effect predominantly associated with the application of higher concentrations. The unpredictability of the response of an individual neuron to somatostatin is partially explained by three phenomena: a marked tachyphylaxis, an inverted U-shaped dose response curve for membrane depolarization, and qualitatively different responses depending on the concentration of somatostatin. These findings show that somatostatin is predominantly an excitatory agent when applied to cortical neurons, but it may cause several different changes in membrane properties. The dose response data suggest a considerable complexity of the actions of somatostatin at a cellular level.

Action Potentials↗
PubMed2001

Interaction with the NMDA receptor locks CaMKII in an active conformation.

Calcium- and calmodulin-dependent protein kinase II (CaMKII) and glutamate receptors are integrally involved in forms of synaptic plasticity that may underlie learning and memory. In the simplest model for long-term potentiation, CaMKII is activated by Ca2+ influx through NMDA (N-methyl-D-aspartate) receptors and then potentiates synaptic efficacy by inducing synaptic insertion and increased single-channel conductance of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Here we show that regulated CaMKII interaction with two sites on the NMDA receptor subunit NR2B provides a mechanism for the glutamate-induced translocation of the kinase to the synapse in hippocampal neurons. This interaction can lead to additional forms of potentiation by: facilitated CaMKII response to synaptic Ca2+; suppression of inhibitory autophosphorylation of CaMKII; and, most notably, direct generation of sustained Ca2+/calmodulin (CaM)-independent (autonomous) kinase activity by a mechanism that is independent of the phosphorylation state. Furthermore, the interaction leads to trapping of CaM that may reduce down-regulation of NMDA receptor activity. CaMKII-NR2B interaction may be prototypical for direct activation of a kinase by its targeting protein.

Animals↗
PubMed1992

Synaptic behaviour in the myenteric plexus of the guinea-pig gastric antrum.

1. Intracellular recording methods were used to study the synaptic behaviour of neurones in the myenteric plexus of the guinea-pig gastric antrum. Synaptic potentials occurred spontaneously or were evoked by focal electrical stimulation of interganglionic fibre tracts. Synaptic events consisted of fast and slow excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). 2. Fast EPSPs with durations less than 20 ms were evoked in every antral neurone in a population sample of 370 cells. Most of the ganglion cells received multiple inputs from axons entering the individual ganglia in several different interganglionic fibre tracts. Many of the neurones also received input from multiple axons projecting in individual fibre tracts. The fast EPSPs behaved like nicotinic cholinergic EPSPs. They were evoked at stimulus frequencies up to 60 Hz without evidence of the run-down characteristic of fast EPSPs in the intestine. 3. Slow EPSPs were evoked by repetitive stimulation of the interganglionic connectives. They consisted of a slowly activating depolarization which persisted for several seconds after termination of the stimulus. The depolarizing responses were associated with an increase in the input resistance, with enhanced excitability and with suppression of hyperpolarizing after-potentials in AH/type 2 neurones. They were observed in 14.4% of the neurones of which 89% were AH/type 2 neurones. AH/type 2 neurones, unlike other myenteric neurones, were identified by action potentials with long lasting after-hyperpolarization. 4. IPSPs were hyperpolarizing potentials evoked by repetitive stimulation of interganglionic fibre tracts. The hyperpolarizing responses were associated with decreased input resistance. They occurred in 1.4% of the antral neurones. 5. Application of acetylcholine (ACh) by micro-ejection mimicked the fast EPSPs in all neurones. This fast nicotinic response to ACh was followed by a slowly activating, long-lasting muscarinic depolarization in 32% of the neurones. The slow muscarinic response was associated with increased input resistance, suppression of hyperpolarizing after-potentials and enhanced excitability. 6. Fast EPSPs were not suppressed by accumulation of ACh at presynaptic transmitter release sites. Unlike the intestine, presynaptic muscarinic autoreceptors appeared to be absent from the microcircuits in the antrum. 7. Synaptic behaviour in the local circuits of the gastric antrum differed from the gastric corpus. This may be a reflection of specialization of the circuits for organization of the distinctive patterns of digestive behaviour found in this region of the stomach.

Action Potentials↗
PubMed2004

An algorithm for real-time extraction of population EPSP and population spike amplitudes from hippocampal field potential recordings.

A new method is presented for extracting the amplitude of excitatory post synaptic potentials (EPSPs) and spikes in real time. It includes a low pass filter (LPF), a differentiator, a threshold function, and an intelligent integrator. It was applied to EPSP and population spike data recorded in the Dentate Gyrus and the CA1 hippocampus in vitro. The accuracy of the extraction algorithm was evaluated via the extraction normalized mean square error (eNMSE) and was found to be very high (eNMSE < 5%). The preservation of neuronal information was confirmed using the Volterra-Poisson modeling approach. Volterra-Poisson kernels were computed using amplitudes extracted with both proposed and traditional methods. The accuracy of the computed kernels and the resulting model was evaluated via the prediction normalized mean square error (pNMSE) and was found to be very high (pNMSE < 5%). The similarity between the kernels computed when the proposed method was used to extract the field potential amplitude and their counterparts when the traditional method was used to extract the field potential amplitude confirms the preservation of the neuronal dynamics. The proposed method represents a new class of real time field potential amplitude extraction algorithms with complexity that can be included in hardware implementations.

Action Potentials↗
PubMed1986

Reorganization of synaptic ultrastructure at facilitated lobster neuromuscular terminals.

Prolonged stimulation of the single excitor axon to the lobster distal accessory flexor muscle in the presence of ouabain caused long-term facilitation at its neuromuscular synapses. Hence the extracellularly recorded synaptic potentials failed less frequently and increased their mean amplitude, compared to the non-facilitated (control) potentials from homologous sites in the contralateral muscle. The fine structure of synaptic terminals between matched pairs of facilitated and control preparations was compared with the aid of serial section electron microscopy. Differences between facilitated and control preparations were similar both when the latter were bathed in normal saline or ouabain-containing saline, suggesting that the changes were related to the electrical stimulation rather than to the presence of ouabain. First, the facilitated terminals were smaller in surface area than the control. Second, the number and size of synaptic contacts in the facilitated terminals resembled those in the control. Third, presynaptic dense bodies or active sites increased in number although their sizes remained unaltered in the facilitated terminal. This increase is attributed to the addition of dense bodies at existing synaptic contacts since synaptic contacts remained constant in number between facilitated and control preparations. Fourth, the number and size of synaptic vesicles were unaffected by prolonged stimulation although there was a redistribution of vesicles such that they appeared to be channelled in distinct streams to synaptic contacts. Fifth, mitochondria increased in number and were situated closer to the dense bodies at facilitated nerve terminals than at control terminals. Overall, these changes denote considerable reorganization of the synaptic terminals associated with elevated transmitter release.

Animals↗
PubMed1982

Central innervation of neurones in the inferior mesenteric ganglion and of the large intestine of the cat.

1. Segmental, lumbar sympathetic outflow to neurones in the cat inferior mesenteric ganglion and to the large intestine were studied. Synaptic responses of neurones in the inferior mesenteric ganglion were recorded intracellularly, in vitro, during electrical stimulation of preganglionic fibres in the lumbar white rami. Synaptic responses consisted of excitatory post-synaptic potentials and/or action potentials.2. None of the neurones tested received synaptic input from spinal cord segment L(1). There was synaptic input from segments L(2)-L(5) of the spinal cord. The strongest synaptic input arose from spinal cord segments L(3) and L(4).3. 42% of the neurones tested received synaptic input from only one spinal cord segment. 54% of the neurones tested received convergent synaptic input from two, three or four adjacent lumbar segments.4. Electrophysiological measurements indicated that the number of preganglionic fibres in any lumbar white ramus communicans which provided synaptic input ranged from one to thirteen. Each lumbar white ramus contained, on average, five preganglionic fibres which provided synaptic input to neurones in the inferior mesenteric ganglion.5. Changes in intraluminal colonic pressure were measured in vivo during electrical stimulation of preganglionic fibres in the different lumbar white rami and lumbar ventral roots. Electrical stimulation of white rami L(3) and L(4) abolished phasic changes in intraluminal colonic pressure and reduced basal pressure to near zero. Electrical stimulation of preganglionic fibres in lumbar ventral roots L(3) and L(4) abolished phasic changes in intraluminal colonic pressure and reduced basal pressure to near zero. Stimulation of ventral roots L(1), L(2) and L(5) had little to no effect on intraluminal pressure.6. Based on the data obtained in this study, two hypotheses are proposed. First, spinal cord segments L(3), L(4) and L(5) are the primary sources of central synaptic input to neurones in the inferior mesenteric ganglion. Secondly, spinal cord segments L(3) and L(4) control colonic motility.

Action Potentials↗
PubMed1981

Transformation of signals by interneurones in the barnacle's visual pathway.

1. The photoreceptors of the median eye of the giant barnacle drive decrementally-conducting neurones in the supraoesophageal ganglion termed ;inverting cells' (I-cells) which in turn drive impulse-producing neurones termed ;amplifying cells' (A-cells). Using intracellular recording techniques we have studied the role of I-cells in visual processing.2. Horseradish peroxidase injections show that I-cells are interneurones whose processes are confined to the regions of the photoreceptor terminals on both sides of the bilaterally symmetrical ganglion.3. In the dark, I-cell membrane potentials (-45 mV) are considerably less negative than those of other ganglion cells (-60 to -70 mV). At the onset of a maintained light, I-cells undergo a transient peak hyperpolarization which declines to a steady-state response. Both response components are graded with light intensity.4. The reversal potential of the peak of the I-cell light response depends on the external K(+) concentration more strongly than does the dark resting potential (3-30 mm-K(+)). This evidence indicates that the hyperpolarization results from an increase in the cell's permeability to K(+) ions.5. At the offset of light an I-cell undergoes a transient depolarization that overshoots the dark membrane potential. Dimming of a background light can also cause the I-cell membrane potential to overshoot its dark resting value. This overshoot is associated with a large depolarizing synaptic potential in A-cells.6. An overshoot of the dark resting potential can also be elicited by the break of a hyperpolarizing pulse of current injected into an I-cell. The amplitude of this overshoot increases with pulse duration over a time course of seconds.7. In the presence of external tetraethylammonium ion (TEA) and tetrodotoxin, (TTX), the break of a hyperpolarizing pulse or the onset of a depolarizing pulse can evoke in an I-cell an action potential whose rate of rise and amplitude depend on the external Ca concentration. This action potential can be maintained by replacement of external Ca with Ba, or blocked by addition of 15 mm-Co to the saline. These observation's indicate that depolarizing potential changes in this cell activate a voltage-sensitive Ca conductance.8. When hyperpolarizing current pulses are injected into an I-cell, the voltage during the pulse sags back slowly towards the dark resting potential. Thus, during hyperpolarization with light or current an I-cell's membrane properties change over a time course of seconds.9. The onset of a depolarizing pulse or the offset of a hyperpolarizing pulse of current injected into an I-cell leads to a transient depolarization of a simultaneously impaled A-cell. Synaptic transmission occurs when the I-cell is depolarized to the vicinity of the dark resting potential. The amplitude of the response in an A-cell depends on the rate of change of the I-cell voltage.

Animals↗
PubMed1988

Modification of nicotinic ganglionic transmission by muscarinic slow postsynaptic potentials in the in vitro rabbit superior cervical ganglion.

The influence of slow muscarinic postsynaptic potentials, i.e., the s-IPSP and s-EPSP, on synaptic transmission mediated through nicotinic receptors was studied in the superior cervical ganglion of the rabbit. Postganglionic spikes and synaptic potentials were elicited by delivery of conditioning and test stimulus pulses to afferent fibers. When paired stimulus volleys were separated by brief intervals (20-100 msec) or long intervals (1,000-8,000 msec), the population spike elicited by the test stimulus was larger in amplitude than that elicited by the conditioning volley. When paired stimulus volleys were separated by 250-500 msec, the amplitude of the population spike elicited by the test volley was smaller than that elicited by the conditioning stimulus. Gallamine, which selectively blocks the s-IPSP, reduced the suppression of the test spike which occurred when stimulus IPIs ranged between 250-500 msec. Pirenzepine, which selectively blocks the s-EPSP, reduced the late facilitation of test postganglionic spikes which occurred with stimulus IPIs greater than 1,000 msec. The non-selective muscarinic antagonist QNB, produced changes in postganglionic spike amplitude that were similar to the combined effects of gallamine and pirenzepine. The evidence indicates that the s-IPSP and s-EPSP modified the excitability state of the ganglionic neurons and subsequent synaptic transmission that was mediated through nicotinic receptors.

Action Potentials↗
PubMed2006

The functional nature of synaptic circuitry is altered in area CA3 of the hippocampus in a mouse model of Down's syndrome.

Down's syndrome (DS) is the most common cause of mental retardation, and memory impairments are more severe in DS than in most if not all other causes of mental retardation. The Ts65Dn mouse, a genetic model of DS, exhibits phenotypes of DS, including memory impairments indicative of hippocampal dysfunction. We examined functional synaptic connectivity in area CA3 of the hippocampus of Ts65Dn mice using organotypic slice cultures as a model. We found reductions in multiple measures of synaptic function in both excitatory and inhibitory inputs to pyramidal neurons in CA3 of the Ts65Dn hippocampus. However, associational synaptic connections between pyramidal neurons were more abundant and more likely to be active rather than silent in the Ts65Dn hippocampus. Synaptic potentiation was normal in these associational connections. Decreased overall functional synaptic input onto pyramidal neurons expressed along with the specific hyperconnectivity of associational connections between pyramidal neurons will result in predictable alterations of CA3 network function, which may contribute to the memory impairments seen in DS.

Animals↗
PubMed1997

Orally projecting interneurones in the guinea-pig small intestine.

1. Orally projecting, cholinergic interneurones are important in mediating ascending excitatory reflexes in the small intestine. We have shown that there is just one major class of orally projecting interneurone, which we have characterized using retrograde labelling in organ culture, combined with immunohistochemistry, intracellular recording and dye filling. 2. Orally projecting interneurones, previously shown to be immunoreactive for choline acetyltransferase, tachykinins, enkephalin, calretinin and neurofilament protein triplet, have axons up to 14 mm long and are the only class of cells with orally directed axons more than 8.5 mm long. 3. They are all small Dogiel type I neurones with short dendrites, usually lamellar in form, and a single axon which sometimes bifurcates. Their axons give rise to short varicose collaterals in myenteric ganglia more than 3 mm oral to their cell bodies. 4. Orally projecting interneurones receive prominent fast excitatory post synaptic potentials (fast EPSPs). A major source of fast EPSPs is other ascending interneurones located further aborally. They also receive fast EPSPs from circumferential pathways. 5. In the stretched preparations used in this study, orally projecting interneurones were highly excitable, firing repeatedly to depolarizing current pulses and had negligible long after-hyperpolarizations following their action potentials. They did not receive measurable non-cholinergic slow excitatory synaptic inputs. 6. Ascending interneurones had a characteristic inflection in their membrane responses to depolarizing current pulses and their first action potential was typically delayed by approximately 30 ms. Under single electrode voltage clamp, ascending interneurones had a transient outward current when depolarized above -70 mV from more hyperpolarized holding potentials. Ascending interneurones also consistently showed marked inward rectification under both current clamp and voltage clamp conditions. 7. This class of cells has consistent morphological, neurochemical and electrophysiological characteristics and are important in mediating orally directed enteric reflexes.

Animals↗
PubMed1985

Prolonged modification of action potential shape by synaptic inputs in molluscan neurones.

1. Somatic action potentials of Lymnaea neurons are modified by excitatory or inhibitory synaptic inputs and have been studied using phase-plane techniques and an action potential duration monitor. 2. Excitatory synaptic inputs increase the rate of neuronal discharge, cause action potential broadening, a decrease in the maximum rate of depolarization (Vd) and a decrease in the maximum rate of repolarization (Vr). 3. Inhibitory synaptic inputs decrease the discharge rate and cause narrowing of action potentials, an increase in Vd and an increase in Vr. 4. The effects reported above outlast the original synaptic inputs by many seconds and, if the somatic action potentials are similar to those in the axon terminals, they may have far-reaching effects on transmitter release.

Action Potentials↗
PubMed1984

On the two subdivisions and intrinsic synaptic connexions in the submandibular ganglion of the rat.

Parasympathetic neurones in the submandibular ganglion of the rat innervate the submandibular and sublingual salivary glands. Neurones which innervate the submandibular gland (s.m. neurones) are usually located along the salivary ducts which drain both glands. Neurones which innervate the sublingual gland (s.l. neurones) are located in the thin sheet of tissue which lies between the salivary ducts and the lingual nerve. The existence and characteristics of intrinsic synaptic connexions were studied electrophysiologically in these two divisions of the submandibular ganglion. Three days or more after denervating the ganglion two types of excitatory intrinsic synaptic potentials--chemical and electrical--were recorded in ganglion cells. Chemical synaptic responses were reversibly blocked by nicotinic antagonists such as hexamethonium (10 microM) and D-tubocurarine (100 microM). Intrinsic chemical synapses were common among s.m. neurones (present in 72% of neurones) but only 12% of s.l. neurones were coupled with chemical synapses. Electrical coupling was found among 31% of s.m. neurones but was not observed between s.l. neurones. Electrotonic coupling in s.m. neurones in denervated and intact ganglia was directly demonstrated by impaling adjacent neurones with separate micro-electrodes. The average coupling ratio for current pulses injected into one cell and recorded in the adjacent cell was 0.06. During the first 30 days after birth, the number of synaptic inputs from preganglionic (chorda tympani) axons was markedly reduced in both s.m. and s.l. neurones, whereas the incidence of electrical synaptic connexions remained unchanged. The effect of long-term denervation (up to 4 months) on intrinsic synapses was examined. The membrane properties of the parasympathetic neurones and the intrinsic synaptic connexions were maintained without marked changes. It is concluded that the submandibular ganglion in the rat consists of two distinct populations of parasympathetic neurones. The two classes of neurones differ in (1) their location within the ganglion, (2) their target organs and (3) the incidence of intrinsic synapses. Possible mechanisms for the development, maintenance and function of these intrinsic synapses are discussed.

Action Potentials↗
PubMed1973

Hair cell interactions in the statocyst of Hermissenda.

Hair cells in the statocyst of Hermissenda crassicornis respond to mechanical stimulation with a short latency (<2 ms) depolarizing generator potential that is followed by hyperpolarization and inhibition of spike activity. Mechanically evoked hyperpolarization and spike inhibition were abolished by cutting the static nerve, repetitive mechanical stimulation, tetrodotoxin (TTX), and Co(++). Since none of these procedures markedly altered the generator potential it was concluded that the hyperpolarization is an inhibitory synaptic potential and not a component of the mechanotransduction process. Intracellular recordings from pairs of hair cells in the same statocyst and in statocysts on opposite sides of the brain revealed that hair cells are connected by chemical and/or electrical synapses. All chemical interactions were inhibitory. Hyperpolarization and spike inhibition result from inhibitory interactions between hair cells in the same and in opposite statocysts.

Animals↗
PubMed1980

Alterations in spontaneous miniature potential activity during habituation of a vertebrate monosynaptic pathway.

Intracellular recordings of spontaneous miniature synaptic potentials were made from motoneurons of the isolated spinal cord of the frog, as a function of habituation of the monosynaptic pathway originating with lateral column fibers. The frequency and amplitude of spontaneous miniature potentials were used to assess the possibility of several proposed mechanisms underlying habituation in this system. These studies provide clear evidence in eliminating the role of transmitter depletion, incomplete vesicle filling and receptor desensitization in the habituation process occurring within this vertebrate central nervous system.

Animals↗
PubMed1993

GABA-immunoreactivity in processes presynaptic to the terminals of afferents from a locust leg proprioceptor.

Individually labelled sensory neurons from the femoral chordotonal organ, a proprioceptor at the femoro-tibial joint of a locust hindleg, were analysed by intracellular recording, and by electron microscopical immunocytochemistry to reveal the arrangement of their input and output synapses and to determine whether the input synapses were GABAergic. Intracellular recordings from these sensory neurons show spikes superimposed on a barrage of synaptic potentials during movements of the femoro-tibial joint. These synaptic inputs can be mimicked by GABA. Input synapses are made onto the vesicle-containing terminals of afferents and are often closely associated with the output synapses. By contrast, the axons of the afferents in the neuropil have no vesicles and neither make nor receive synapses. The input synapses to the afferent terminals are made from processes typically a few microns in diameter, whereas the output synapses are made onto much smaller processes of only 0.1-0.2 micron. Input synapses at which an afferent terminal is the only postsynaptic element are common. Where the synapse is dyadic the second postsynaptic element does not usually appear to be a chordotonal afferent. The output synapses from the afferent terminals are usually dyadic. At 78% of the input synapses, the presynaptic neurite showed immunoreactivity to a GABA antibody, supporting the physiological evidence that the presynaptic effects can be mediated by the release of GABA. The remaining (22%) immunonegative synapses are intermingled with those showing GABA immunoreactivity, but their putative transmitter is unknown. These morphological observations suggest that the presynaptic control of the chordotonal afferents is largely mediated by GABAergic neurons, but because other types of neuron also appear to be involved, presynaptic modulation may be more complex than has yet been revealed by the physiology.

Action Potentials↗
PubMed1992

Induction of giant depolarizing potentials by zinc in area CA1 of the rat hippocampus does not result from block of GABAB receptors.

The possibility that zinc (Zn2+) induces giant depolarizing potentials (GDPs) by blocking pre- and postsynaptic gamma-aminobutyric acidB (GABAB) receptors in area CA1 of rat hippocampal slices was investigated. Monosynaptic GABAA receptor-mediated fast and GABAB receptor-mediated late inhibitory postsynaptic potentials (IPSPs) were evoked in the presence of the excitatory amino acid (EAA) receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-amino-5-phosphonovalerate (APV). Addition of Zn2+ (0.3 mM) resulted in the appearance of long-lasting GDPs which obscured monosynaptic late IPSPs. The GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) blocked fast monosynaptic IPSPs and GDPs, revealing a monosynaptic late IPSP that was prolonged in the presence of Zn2+ and blocked by the GABAB receptor antagonist CGP 35,348 (100 microM). The selective GABAB receptor agonist baclofen (10 microM) depressed monosynaptic IPSPs and population excitatory postsynaptic potentials (pEPSPs) by acting at presynaptic GABAB receptors. Depression of synaptic potentials by baclofen was unaffected by Zn2+. These results suggest that induction of GDPs in area CA1 does not result from an action of Zn2+ at GABAB receptors. We suggest instead that Zn2+ induces GDPs by inducing synchronized discharge of GABAergic interneurons.

2-Amino-5-phosphonovalerate↗
PubMed1983

Generation of respiratory activity by the lamprey brain exposed to picrotoxin and strychnine, and weak synaptic inhibition in motoneurons.

The roles of Cl-dependent synaptic inhibition in the generation of fictive breathing were tested in isolated brains of adult lampreys, Ichthyomyzon unicuspis. Only a few inhibitory synaptic potentials were recorded in respiratory motoneurons between excitatory bursts. This was also true after Cl- injections inverted them to depolarizing potentials. A weak and variable phase of Cl-sensitive synaptic inhibition occurred at the ends of excitatory bursts. Respiratory motoneurons had a pronounced post-spike hyperpolarization, which was distinct from synaptic inhibition and appeared to be a more important mechanism for termination of firing. The production of the basic rhythm for respiration was tested in strychnine, picrotoxin, bicuculline and Cl-free fluid. Low concentrations of the blocking drugs prevented the inhibitory effects of bath-applied glycine and gamma-aminobutyric acid, but essentially normal respiratory bursts still occurred. Equilibration of isolated brains in high concentrations of strychnine and picrotoxin did not prevent periodic activities, but burst durations were increased and inter-burst intervals were longer and less regular than normal. Similar bursts could also occur transiently in Cl-free fluid. Recordings from the IX and X motor nuclei indicated that respiratory neurons produced the periodic bursts in the presence of strychnine and picrotoxin. Hemisections of the brain behind the V motor nuclei eliminated the bursts ipsilaterally. This indicated that descending excitation was necessary during pattern generation both in normal fluid and in the presence of antagonists of synaptic inhibition. Conventional synaptic inhibition does not appear to be essential for respiratory pattern generation in the adult lamprey but may contribute to its modulation. The hypothetical neural oscillator may consist of excitatory bursting interneurons.

Animals↗