Long-lasting Inhibitory Postsynaptic Potential Research Articles

SL1 Neuropharmacology of intracortical inhibition

Inhibition in the cerebral cortex is essential for regulating cortical excitability and plasticity and is mediated by gamma-amino butyric acid receptors (GABAR). Two principle forms of GABARs exist: GABAARs and GABABRs which mediate short-lasting vs. long-lasting inhibitory postsynaptic potentials, respectively, and are activated by different ligands. The GABAARs can be divided into subtypes of alpha-1 6 subunit bearing receptors which are located on different populations of highly specialized inhibitory interneurons and which are responsible for different functions: for example, activation of the alpha-1 GABAAR has sedative and anticonvulsant effects while activation of the alpha-2 GABAAR results in anxiolytic effects. Classical benzodiazepines (such as diazepam) have high affinity to alpha-1, -2, -3 and -5 GABAARs, zolpidem has highest affinity to the alpha-1 GABAAR, low-doses of ethanol activate alpha-4 and -6 GABAARs in the cerebellum and baclofen is a specific GABABR agonist. Transcranial magnetic stimulation (TMS) allows testing of motor cortical inhibition. Two protocols are available which measure GABAAR mediated short-interval intracortical inhibition (SICI) and GABABR mediated long-interval intracortical inhibition (LICI). Accordingly, classical benzodiazepines enhance SICI while baclofen increases LICI. More advanced pharmacological testing of SICI with classical benzodiazepines vs. zolpidem showed that SICI is most likely mediated by the alpha-2 GABAAR. Therefore, TMS offers the opportunity to measure motor cortical inhibition mediated by the various subtypes of the GABAR. This is of strong interest for drug development, but also for measuring disordered inhibition in neurological or psychiatric diseases such as epilepsy or schizophrenia. This special lecture will provide an upto-date overview on the neuropharmacology of intracortical inhibition as measured by TMS and its clinical and research applications.

Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus

The dentate gyrus (DG) is a gateway that regulates seizure activity in the hippocampus. We investigated the site of action of lamotrigine (LTG), an effective anticonvulsant, in the regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated excitatory synaptic transmission on DG. Evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (eEPSCampa and eEPSCnmda) were recorded by whole-cell patch-clamp recording from the granule cells of DG in brain slice preparation of young Wistar rats (60-120 g). Exogenously applied AMPA and NMDA-induced currents and AMPA receptor-mediated miniature EPSC (mEPSCampa) were recorded in the presence of specific antagonists. LTG inhibited both eEPSCampa and eEPSCnmda, and had no effect on exogenously applied NMDA-induced current indicating LTG inhibited glutamate release. Previous studies demonstrated that alteration in glutamate concentration in synaptic cleft causes parallel changes of eEPSCampa and eEPSCnmda. Our results showed that LTG inhibited eEPSCampa significantly more than eEPSCnmda (p < 0.05), suggesting that LTG may also have blocked the postsynaptic AMPA receptor. The hypothesis is further supported by the facts that; (1) LTG (30-100 microM) inhibited direct exogenously applied AMPA-induced currents (to 90%), (2) LTG significantly reduced the amplitude, but not the frequency of mEPSCampa and asynchronous (EPSC), and (3) LTG-induced reduction of eEPSCampa was not associated with a modification of the paired-pulse ratio. To sum up, LTG exerts a postsynaptic inhibitory mechanism on the AMPA receptor. Our results demonstrate that LTG suppresses postsynaptic AMPA receptors and reduces glutamate release in granule cells of DG. The postsynaptic effect can be one of the underlying mechanisms of LTG's anticonvulsant action.

Long-term alteration of gamma-aminobutyric acid B receptor subunits in immature rats after recurrent febrile seizures

Febrile seizure (FS) is closely related to an altered transmission of gamma-aminobutyric acid (GABA). GABA exerts its effects through ionotropic receptors (GABA(AR) and GABA(CR)) and metabotropic receptors (GABA(BR)). GABA(BRs) are located at pre- and postsynaptic sites. Stimulation of postsynaptic receptors generates long-lasting inhibitory postsynaptic potentials (IPSPs) that are important for the fine-tuning of inhibitory neurotransmission and caused by an increase in K(+) conductance. At presynaptic sites, GABA(BRs) mediate a suppression on the release of neurotransmitters such as of GABA or glutamate by inhibiting voltage-sensitive Ca(2+) channels. The present study aimed to explore the long-term changes of GABA(B) receptor subunits in immature rats after recurrent febrile seizures. Rats were randomly divided into control group and hyperthermia treatment group. The control rats (n = 64) were put into 37 degrees C water for 5 minutes. Rats with hyperthermia treatment were put into 44.8 degrees C water for 5 minutes. If a rat in hyperthermia treatment group showed seizure within 5 min, the rat was taken out of the water as soon as the seizure occurred. Water-immersion was carried out 10 times, once every 2 days. Rats showing 10 seizures (FS(10), n = 64) were studied. Rats exposed to hyperthermia for 10 times without seizure were also studied as hyperthermia-only (H, n = 64) group. Rats showing one seizure at the last time of 10 times of hyperthermia treatment were studied as one-seizure group (FS(1), n = 64). The other rats were studied for other research. The changes of GABA(B)R(1) and GABA(B)R(2) co-localization were detected by double fluorescence;the quantitative alteration of GABA(B)R(1) and GABA(B)R(2) were detected by quantitative RT-PCR; the binding of GABA(B)R(2) to GABA(B)R(1) was detected by immunoprecipitation/Western blot. GABA(B)R(1), GABA(B)R(2), and the binding of GABA(B)R(2) to GABA(B)R(1) decreased after the last febrile seizure in FS(10) group, the expression of GABA(B)R(1) returned to normal in later phase while GABA(B)R(2) and the binding of them did not. Recurrent FS down-regulated the expression of GABA(B)R subunits in a long term.

The mormyromast region of the mormyrid electrosensory lobe. II. Responses to input from central sources.

This is the second in a series of two papers on the mormyromast regions of the electrosensory lobe (ELL) of mormyrid electric fish. In this study, we examined the effects of artificial stimulation of two of the three major central inputs to ELL on different morphologically identified cell types of ELL. The three major central inputs to ELL are the eminentia granularis posterior, the juxtalobar nucleus, and the preeminential nucleus. We stimulated the juxtalobar and preeminential nuclei. We compared the effects of such stimulation with effects of the electric organ corollary discharge (EOCD) on the same cells to understand the origins of EOCD effects in ELL. Responses to juxtalobar stimulation were different in different cell types and remarkably similar to corollary discharge responses in the same cells. In addition, responses to juxtalobar stimulation were consistently depressed when the stimulus was delivered immediately after the naturally occurring EOCD response. These findings indicate that the juxtalobar nucleus is a major source of the EOCD responses of ELL cells. In contrast, preeminential stimulation evoked similar responses in medium ganglionic cells, and the two types of efferent cells that were quite different from the EOCD responses of these cells, suggesting that the preeminential nucleus is less important than the juxtalobar nucleus in determining the EOCD responses of ELL cells. Preeminential responses of medium ganglionic and efferent cells consisted of a short-latency excitatory postsynaptic potential (EPSP) followed by a long-lasting inhibitory postsynaptic potential (IPSP). Both the EPSPs and IPSPs were facilitated when brief bursts of closely spaced stimuli were delivered.

Electrophysiology of cat association cortical cells in vivo: intrinsic properties and synaptic responses.

1. The intrinsic properties and synaptic responses of association cortical neurons (n = 179) recorded from cat's areas 5 and 7 were studied in vivo. Intracellular recordings were performed under urethane anesthesia. Resting membrane potential (Vm) was -71.7 +/- 1.2 (SE) mV, amplitude of action potential was 83.7 +/- 2.3 mV, and input resistance was 18.4 +/- 1.8 M omega. Cells were identified ortho- and antidromically from lateroposterior and centrolateral thalamic nuclei and from homotopic foci in the contralateral cortex. Physiologically identified neurons were intracellularly stained with Lucifer yellow (LY) and found to be pyramidal-shaped elements (n = 21). 2. We classified the neurons as regular-spiking and intrinsically bursting cells. Regular-spiking cells were further classified as slow- and fast-adapting according to the adaptation of spike frequency during long-lasting depolarizing current pulses. 3. Regular-spiking, slow-adapting neurons had a monophasic afterhyperpolarization (AHP) or a biphasic AHP with fast and medium components (FAHP, mAHP). Slow-adapting behavior was observed in 84% (n = 119) of the regular-spiking cells. 4. Regular-spiking, fast-adapting cells only fired a train of spikes at the beginning of the pulse. Thereafter, the Vm remained as a depolarizing plateau, occasionally triggering some spikes. These neurons had a monophasic AHP and represented 16% (n = 23) of the regular-spiking neurons. 5. Intrinsically bursting neurons (n = 37) were observed in 20% of neocortical cells at depolarized Vm. Their action potential was followed by a marked depolarizing afterpotential (DAP). Rhythmic (4-10 Hz) bursts occurred during long-lasting depolarizing current pulses. 6. Small (3-10 mV), fast (1.5-4 ms), all-or-none depolarizing potentials were triggered by depolarizing current pulses. They are tentatively regarded as dendritic spikes recorded from the soma because their rate of occurrence changed as a function of the Vm and they were eventually blocked by hyperpolarization. 7. Synaptic stimulation of either thalamic or homotopic contralateral cortical areas elicited a sequence of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). Two components of the EPSP were revealed. At a hyperpolarized Vm, the initial component of the EPSP increased in amplitude, whereas the secondary component was blocked. Repetitive (10 Hz) stimulation of the thalamus or contralateral cortex elicited incremental responses. The augmentation phenomenon was due to an increase in the secondary component of the EPSP. The cortically elicited augmenting responses survived extensive thalamic lesions. A short IPSP and a long-lasting IPSP were evoked by thalamic or cortical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring the excitability of neocortical efferent neurons to direct activation by extracellular current pulses.

1. Extracellular action potentials were recorded from antidromically activated efferent neurons in visual, somatosensory, and motor cortex of the awake rabbit using low-impedance metal microelectrodes. Efferent neurons were also activated by current pulses delivered near the soma [juxtasomal current pulses (JSCPs)] through the recording microelectrode. Action potentials generated by JSCPs were not directly observed (because of the stimulus artifact), but were inferred with the use of a collision paradigm. Efferent populations studied include callosal neurons [CC (n = 80)], ipsilateral corticocortical neurons [C-IC (n = 21)], corticothalamic neurons of layer 6 [CF-6 (n = 57)], and descending corticofugal neurons of layer 5 [CF-5, corticotectal neurons of the visual cortex (n = 48)]. 2. Most CC neurons (45/46) and all C-IC (8/8) and CF-6 neurons (39/39) were directly activated by JSCPs at near-threshold intensities. Some CF-5 neurons (9/38), however, showed evidence of indirect activation. All efferent classes had similar current thresholds (means 1.85-2.10 microA) to direct activation by JSCPs, and thresholds were inversely related to extracellular spike amplitude. For each neuron, the range of JSCP intensities that generated response probabilities of between 0.2 and 0.8 was measured, and this "range of uncertainty" was significantly greater in CF-5 neurons (mean 32.7% of threshold) than in CC (mean 19.0%) or CF-6 (mean 20.4%) neurons. 3. Several factors indicate that the threshold of efferent neurons to JSCPs is very sensitive to excitatory and inhibitory synaptic inputs. Iontophoretic applications of gamma-aminobutyric acid (GABA) increased the threshold to JSCPs, and glutamate reduced the threshold. Electrical stimulation of afferent pathways at intensities just below threshold for eliciting action potentials resulted in a dramatic decrease in JSCP threshold. This initial short-latency threshold decrease was specific to stimulation of particular afferent pathways and is thought to reflect excitability changes associated with EPSPs. Examination of such subliminal responses revealed subthreshold synaptic inputs that were not revealed by examination of all-or-none action potentials. In contrast to the specificity of the short-latency threshold decrease, a long-lasting increase in JSCP threshold was seen in virtually all neurons after stimulation of each of the afferent pathways tested. This increase in threshold usually began 20-40 ms after stimulation, lasted for 100-200 ms, and is thought to reflect excitability changes associated with a long-lasting inhibitory postsynaptic potential (IPSP) seen in many cortical neurons. 4. Many neurons in primary somatosensory cortex of rat, cat, and rabbit have no demonstrable receptive fields.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypoxia-induced functional alterations in adult rat neocortex.

1. Brief periods of hypoxia (2-7 min) were induced in rat neocortical slices maintained in an interface-type recording chamber at 34-35 degrees C by changing the aerating gas from 95% O2-5% CO2 to 95% N2-5% CO2. Field potential (FP) and intracellular recordings were obtained in layers II/III of primary somatosensory cortex. Intracellular injection of biocytin revealed the characteristic morphology of supragranular spiny pyramidal neurons. 2. Excitatory synaptic transmission reversibly decreased by 45% as estimated from FP responses to orthodromic stimulation of the underlying white matter/layer VI. Excitatory postsynaptic potentials (EPSPs) were suppressed by 36% in amplitude and recovered within 2-3 min after reoxygenation. During the recovery period, EPSPs showed a reversible increase in duration by 72%. 3. Inhibitory synaptic transmission was completely blocked as determined in FP responses with a paired-pulse inhibition protocol. The fast inhibitory postsynaptic potential (IPSP) declined by 58% during hypoxia. The long-lasting IPSP was suppressed by 75% and showed incomplete recovery. During hypoxia, the amplitude of both IPSPs was significantly more strongly suppressed than the EPSP. 4. In 40% of the cells, hypoxia induced an early anoxic hyperpolarization with a reversal potential of E = -80.8 mV, followed by a postanoxic hyperpolarization (E = -89.4 mV). In a second group of cells (37%), a gradual anoxic depolarization with E = -57.5 mV was observed instead of an early hyperpolarization. In both groups of cells, the anoxic response was associated with a marked decrease in input resistance, by 42 and 31%, respectively. 5. The spike discharge frequency was reversibly suppressed by 71% during hypoxia. A transient hyperexcitability accompanied with a rise in input resistance and discharge rate was observed in 38% of the cells on reoxygenation. 6. The reversal potential of the anoxic hyperpolarization was unaffected by tetrodotoxin (TTX) but was significantly altered by application of the ATP-sensitive K+ channel (KATP) blocker gliquidone. Application of gliquidone additionally resulted in a significantly smaller hypoxia-induced decline in paired-pulse inhibition. 7. Increases in tissue high-energy phosphates induced by preincubating the slices in 25 mM creatine for greater than 2 h had a pronounced protective effect on excitatory and inhibitory synaptic transmission. 8. These data suggest a selective vulnerability of the neocortical inhibitory system during hypoxia. Our results further indicate that hypoxia activates a pre- and postsynaptic KATP conductance because of the decline in intracellular ATP.

Chapter 8 GABAA and pre- and post-synaptic GABAB receptor-mediated responses in the lateral geniculate nucleus

Publisher Summary This chapter reviews the results that have emerged in past years from the electrophysiological studies concerning the action of gamma-aminobutyric acid (GABA) in in vitro slices of the ventral-lateral geniculate nucleus (vLGN) and dorsal-lateral geniculate nucleus (dLGN) of cats and rats. In particular, the effects of pre- and post-synaptic GABA B receptor activation help to appreciate the variety of responses that GABA can generate in the visual thalamus. Pre-synaptic GABA B receptors exert a negative control on GABA and glutamate release, while the activation of post-synaptic GABA B receptors present on thalamocortical (TC) cells evokes a late, long-lasting inhibitory post-synaptic potential that is responsible for a weak inhibition as well as for burst-firing excitation of these cells. In the cat, visual information from the retina to the visual cortex via the dLGN is carried in three largely independent and segregated channels—the X, Y, and W pathways. TC cells in each of these groups possess many features that are different from those of the other groups, such as cell morphology, laminar distribution, synaptic connections, and visual response properties. TC cells of all three groups, however, receive their visual information through the terminals of optic-tract fibers and send their axons to cells of the visual cortex.

Synaptic efficacy of inhibitory synapses in the reinnervating hypoglossal motoneurons

The synaptic efficacy of inhibitory synapses in tongue protruder motoneurons reinnervating the tongue retractor muscle was studied in cats. We have demonstrated that the percentage magnitude of a short- and a long-lasting inhibitory postsynaptic potential in the inhibitory postsynaptic potentials produced in the tongue protruder motoneurons, whose axons had been cut but allowed to regenerate to make functional contact with the tongue retractor muscles, by lingual nerve or inferior alveolar nerve stimulation, was rearranged to appear like that exhibited by the tongue retractor motoneurons that normally supply that muscle. In addition, the peak amplitude of the summated afterhyperpolarization in a tongue protruder motoneuron on operated cats at nine months axon-union was in the normal range.

Optic tract stimulation evokes GABA A but not GABA B IPSPs in the rat ventral lateral geniculate nucleus

The inhibitory postsynaptic potentials (IPSPs) evoked in neurons of the rat ventral lateral geniculate nucleus (vLGN) by electrical stimulation of the optic tract and the action of GABA and baclofen on the same cells were studied using intracellular recording techniques in an in vitro slice preparation. A short latency short duration IPSP always followed the monosynaptic excitatory postsynaptic potential (EPSP). This IPSP reversed in polarity at about -65mV and was reversibly blocked by bicuculline (50 μM) thus indicating that it represents a GABA A receptor-mediated IPSP. No long-lasting IPSP was evoked in vLGN cells by stimulation of the optic tract, while in the same slice, long-lasting GABA B IPSPs were routinely recorded in the dorsal lateral geniculate nucleus. GABA applied by ionophoresis evoked a hyperpolarization that had a reversal potential close to -70 mV and was antagonized by bicuculline. Baclofen hyperpolarized vLGN neurons and its action was reversibly blocked by the selective GABA B antagonist phaclofen (1 mM). In the presence of bicuculline GABA also produced a hyperpolarization that had properties similar to that evoked by baclofen. These results indicate that, although functional GABA A and GABA B receptors are present on vLGN neurons, stimulation of the optic tract evokes only GABA A but not GABA B mediated IPSPs. The lack of long-lasting GABA B IPSPs could explain the absence of long-lasting inhibition observed in vLGN neurons in vivo following stimulation of the optic tract.

Excitatory inputs to cerebellar dentate nucleus neurons from the cerebral cortex in the cat.

1. In anesthetized cats, we investigated excitatory and inhibitory inputs from the cerebral cortex to dentate nucleus neurons (DNNs) and determined the pathways responsible for mediating these inputs to DNNs. 2. Intracellular recordings were made from 201 DNNs whose locations were histologically determined. These neurons were identified as efferent DNNs by their antidromic responses to stimulation of the contralateral red nucleus (RN). Stimulation of the contralateral pericruciate cortex produced excitatory postsynaptic potentials (EPSPs) followed by long-lasting inhibitory postsynaptic potentials (IPSPs) in DNNs. The most effective stimulating sites for inducing these responses were observed in the medial portion (area 6) and its adjacent middle portion (area 4) of the precruciate gyrus. Convergence of cerebral inputs from area 4 and area 6 to single DNNs was rare. 3. To determine the precerebellar nuclei responsible for mediation of the cerebral inputs to the dentate nucleus (DN), we examined the effects of stimulation of the pontine nucleus (PN), the nucleus reticularis tegmenti pontis (NRTP) and the inferior olive (IO). Systematic mapping was made in the NRTP and the PN to find effective low-threshold stimulating sites for evoking monosynaptic EPSPs in DNNs. Stimulation of either the PN or the NRTP produced monosynaptic EPSPs and polysynaptic IPSPs in DNNs. Using a conditioning-testing paradigm (a conditioning stimulus to the cerebral peduncle (CP) and a test stimulus to the PN or the NRTP) and intracellular recordings from DNNs, we tested cerebral effects on neurons in the PN and the NRTP making a monosynaptic connection with DNNs. Conditioning stimulation of the CP facilitated PN- and NRTP-induced monosynaptic EPSPs in DNNs. This spatial facilitation indicated that the excitatory inputs from the cerebral cortex to DNNs are at least partly relayed via the PN and the NRTP. 4. Stimulation of the contralateral IO produced monosynaptic EPSPs and polysynaptic IPSPs in DNNs. These monosynaptic EPSPs were facilitated by conditioning stimulation of the CP, strongly suggesting that the IO is partly responsible for mediating excitatory inputs from the cerebral cortex to the DN. A comparison was made between the latencies of IO-evoked IPSPs in DNNs and the latencies of IO-evoked complex spikes in Purkinje cells. Such a comparison indicated that the shortest-latency IPSPs evoked from the IO were not mediated via the Purkinje cells and suggested the pathway mediated by inhibitory interneurons in the DN.(ABSTRACT TRUNCATED AT 400 WORDS)

Cortically and lingually induced postsynaptic potentials in trigeminal motoneurons after axotomy.

The membrane properties and the efficacy of excitatory and inhibitory synapses were studied in cat masseteric motoneurons (Mass Mns) after axotomy. In axotomized Mass Mns the slope of the primary range in the frequency-current relationship showed a higher gain than that of normal Mass Mns. The safety of antidromic invasion was increased and the initial segment component of antidromic action potentials could not be separated from the soma-dendritic component. In normal Mass Mns a single shock delivered to the orbital gyrus or the lingual nerve induced long-lasting inhibitory postsynaptic potentials (IPSPs). In two-thirds of Mass Mns explored 30 days after axotomy, a single shock delivered to the orbital gyrus or the lingual nerve evoked a mixture of inhibitory and excitatory synaptic potentials. In Mass Mns 50 days after axotomy, we have demonstrated that the major fraction of the total sample of explored Mass Mns showed long-lasting excitatory postsynaptic potentials followed by IPSPs. The results suggest that in Mass Mns, axotomy is followed by the decline of synaptic efficacy of inhibitory rather than of excitatory synapses.

Abolition of spindle oscillations in thalamic neurons disconnected from nucleus reticularis thalami.

The effects of depriving thalamic relay and intralaminar nuclei from their reticularis thalami (RE) inputs were investigated in acute and chronic experiments on cat. In acutely prepared animals, two (frontal and parasagittal) thalamic transections were made; extracellular and intracellular recordings were performed in RE-disconnected thalamic nuclei. In chronic experiments, the RE nuclear complex was lesioned by means of kainic acid injections; the activity of RE-deprived thalamocortical neurons was extracellularly studied during wakefulness and synchronized sleep. Two features distinguish RE-deprived nuclei from normal thalamic nuclei: absence of spindle-wave rhythmicity and all-burst activity of neurons. The abolition of spindle-related rhythms (sequences of 7- to 14-Hz waves recurring periodically with a rhythm of 0.1-0.2 Hz) in RE-disconnected thalamic nuclei and ipsilateral neocortical areas contrasted with normal spindling rhythmicity in contralateral EEG leads. Spontaneously occurring, rhythmic, long-lasting inhibitory postsynaptic potentials (IPSPs), as observed in intact preparations, were no longer observed in RE-disconnected thalamic neurons. The remaining inhibitory events consisted of short-duration IPSPs. The possibility that RE nucleus is a pacemaker for spindling rhythms, imposing them through inhibitory projections to target thalamic areas, is supported by our concurrent experiments that indicate RE neurons preserve their rhythmicity after disconnection from their major (cortical and thalamic) input sources. RE-deprived thalamocortical neurons exclusively exhibit high-frequency spike bursts whose intrinsic structure is identical to that of intact thalamic relay cells. Instead of the spindle-related sequences of bursts seen in normal animals, the bursts of RE-disconnected thalamocortical neurons are single events, with a dramatic rhythmicity at 1-2 Hz. The presumed mechanism of this rhythmicity is the periodic activation of a low-threshold somatic conductance whose deinactivation is brought about by temporal integration of short-lasting IPSPs. It is known that high-frequency spike bursts of thalamic relay neurons result from hyperpolarization of cell membrane. We blocked the underlying inhibitory events by bicuculline and reversibly changed the all-burst activity of RE-disconnected neurons into a tonic mode. Since the only activity of RE-deprived thalamocortical neurons consists of burst discharges, we hypothesize that local-circuit GABAergic neurons are released from inhibition after RE disconnection or lesion.

Analysis of association fiber system in piriform cortex with intracellular recording and staining techniques.

The piriform cortex of the opossum has been studied with intracellular recording and staining techniques. The experiments were designed to investigate the association fiber system, but the results have also revealed new properties of the afferent fiber system from the olfactory bulb and the inhibitory systems within the piriform cortex. Following shock stimulation of the lateral olfactory tract (LOT), the response of pyramidal cells consists of an initial excitatory postsynaptic potential (EPSP) followed by a long-lasting inhibitory postsynaptic potential (IPSP). The LOT-evoked EPSP consists of two components: an initial monosynaptic followed by a disynaptic component. The monosynaptic EPSP can be isolated by the use of conditioning LOT shocks to block the IPSP and disynaptic EPSP. The disynaptic EPSP can be demonstrated by cutting LOT fibers at the surface of the cortex to eliminate the monosynaptic EPSP and by the use of bicuculline to block the IPSP. The latency of the IPSP is sufficiently brief so that the disynaptic EPSP is blocked at presumed intrasomatic recording sites unless these experimental manipulations are carried out. In all histologically verified pyramidal cells in both layers II and III in which the appropriate tests were carried out, both mono- and disynaptic EPSP components were present. It was concluded on the basis of anatomical considerations, however, that a small number of pyramidal cells would be expected to receive only a disynaptic EPSP. Evidence that the LOT-evoked disynaptic EPSP is mediated, at least in part, by association axons was provided by direct stimulation of these fibers in layer III and by demonstrating that the EPSP is present distal to cuts that sever LOT axons. Direct stimulation of association axons in layer III evokes both a monosynaptic EPSP and a disynaptic IPSP in pyramidal cells at similar latencies. This IPSP is indistinguishable in properties from that evoked by LOT stimulation. Indirect evidence indicates that it is mediated via both feedforward and feedback mechanisms. In most neurons the association fiber-evoked EPSP is masked by the IPSP in response to single deep shocks but can be demonstrated by blocking the IPSP with a preceding LOT shock or by application of bicuculline. Intracellular injection of horseradish peroxidase (HRP) revealed that pyramidal cell axons give rise to an extensive system of local collaterals with a large number of synaptic terminal-like swellings in layer III. It is postulated that these collaterals synapse on both pyramidal and nonpyramidal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic efficacy of inhibitory synapses in hypoglossal motoneurons after transection of the hypoglossal nerves

In cat hypoglossal motoneurons after axotomy the synaptic efficacy of inhibitory synapses made by the lingual nerve afferent fibers was studied. The amplitude of the short- and the long-lasting inhibitory postsynaptic potential produced in tongue protruder motoneurons 24 days after axotomy by stimulation of the lingual nerve was significantly reduced in size as compared with the control on the unoperated side. In most protruder motoneurons 40 days after axotomy a large excitatory postsynaptic potential and a spike was produced by stimulation of either the ipsilateral or the contralateral lingual nerve. We have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was more prominent than that for the long-lasting inhibitory potential in the motoneuron 24 days after axotomy. After the cut axons of protruder motoneurons were reunited to tongue muscles, we have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was less prominent than that in axotomized protruder motoneurons.

Inhibitory postsynaptic potentials evoked in hypoglossal motoneurons by lingual nerve stimulation

The percent magnitude of a short- and a long-lasting inhibitory postsynaptic potential (IPSP) produced in tongue retractor and protruder motoneurons by lingual nerve stimulation was studied in cats. In the retractor motoneurons, stimulation of the ipsilateral lingual nerve produced primarily the short-lasting IPSP, and the neurons had received synaptic input primarily from the afferent fibers in the contralateral lingual nerve generating the long-lasting IPSP. In the protruder motoneurons, in contrast, there was no pronounced difference in the IPSP patterns evoked by stimulation of the ipsilateral and contralateral lingual nerve.

Lingually induced inhibitory postsynaptic potentials in hypoglossal motoneurons after axotomy

Inhibitory postsynaptic potentials (IPSPs) produced in axotomized hypoglossal motoneurons by stimulation of the lingual nerve were explored in cats. In the ipsilateral lingual afferent synapses, the effectiveness of inhibitory synapses for the long-lasting IPSP was diminished in axotomized hypoglossal motoneurons earlier after transection of the hypoglossal nerves, than the effectiveness of inhibitory synapses for the short-lasting IPSP.

Two components of inhibitory postsynaptic potentials evoked in hypoglossal motoneurons by lingual nerve stimulation

The properties of inhibitory postsynaptic potentials (IPSPs) produced in hypoglossal motoneurons by lingual nerve stimulation were explored. In many motoneurons innervating protruder and retractor tongue muscles, IPSPs produced by lingual nerve stimulation were the composite of a short- and a long-lasting IPSP. The short-lasting IPSP was reversed to a depolarizing potential by displacing the membrane potential toward hyperpolarization and by increasing the intracellular concentration of chloride. However, no reversal of the long-lasting IPSP was obtained when the cell membrane was hyperpolarized. The short-lasting IPSP was blocked by the administration of strychnine, but the long-lasting IPSP was insensitive to strychnine and it was selectively blocked by the administration of picrotoxin. When the lingual nerve was stimulated by double shocks separated by about 70-ms intervals, it was found that the second shock produced only a short-lasting IPSP.

Forms of Spontaneous and Evoked Postsynaptic Potentials of Cortical Nerve Cells

Publisher Summary This chapter describes the different forms of spontaneous and evoked postsynaptic potentials of cortical nerve cells. Several factors determine the shapes and sizes of the postsynaptic potentials of nerve cells, such as (1) the amount of transmitter liberated by an impulse, (2) the total synaptic area occupied by the axo-soma-dendritic contacts arising from one single afferent fiber, (3) the membrane resistance, and (4) the location of the synapse relative to the soma. Excitatory postsynaptic potentials (EPSPs) may be due to either the slightly asynchronous activity of many small EPSPs so that single steps cannot be discriminated or the activity of individual fibers with multiple contacts far from the soma. EPSPs after ventralis lateralis (VL) stimulation are cut off by the subsequent inhibitory postsynaptic potential (IPSP). Only with weak stimulation, it is possible to obtain isolated single EPSPs. The limitation of an interpretation of cortical EPSPs in terms of shape indices is discussed in the chapter. Individual IPSPs can be of a short duration. The long-lasting IPSPs usually observed are composite in nature. Contralateral stimulation leads to slowly summating IPSPs. The different forms and shapes of cortical IPSPs can be satisfactorily explained by their summating behavior.