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Electrophysiological studies on the postnatal development of intracerebellar nuclei neurons in rat cerebellar slices maintained in vitro. I. Postsynaptic potentials.

The development of the synaptic responses of intracerebellar nuclei neurons was studied in the rat by the use of thick sagittal cerebellar slices maintained in vitro. It has been shown that functional excitatory synapses are present on these neurons from birth, probably due to climbing and/or mossy fiber collaterals; functional inhibitory synapses, due to monosynaptic projections of Purkinje cell axons onto intracerebellar nuclei, are present as early as postnatal day 2; and a more complex pattern of synaptic responses, including short latency excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs), longer latency IPSPs, and late depolarizing responses, can be elicited in nuclear neurons as early as postnatal day 3, indicating an early development of some complete functional cerebellar circuits involving the intracerebellar nuclei.

Animals↗

Synaptic transmission from muscle afferents during fictive locomotion in the mesencephalic cat.

Modulation of synaptic potentials produced by electrical stimulation of low-threshold muscle afferents in lumbar alpha-motoneurons innervating knee and ankle muscles was studied by intracellular recording during "fictive locomotion" induced by stimulating the mesencephalic locomotor region (MLR) in paralyzed, mesencephalic cats. Averaging postsynaptic potentials in different phases of the fictive step cycle indicated that relatively little amplitude modulation occurred. In nearly half of the 38 motoneurons analyzed, there was a statistically significant tendency for excitatory postsynaptic potentials (EPSPs) to increase in amplitude during the depolarized phase of the oscillation in the membrane potential produced during fictive locomotion (locomotor-drive potential). In 8% the EPSPs decreased under the same conditions, while the rest displayed a constant amplitude during all phases of the fictive step cycle. Only three cells showed a distinct second peak in the EPSP at a latency consistent with transmission in a di- or trisynaptic pathway. Late inhibitory postsynaptic potentials (IPSPs) were also rarely observed. Thus oligosynaptic pathways from muscle afferents to the motoneuron groups studied are not prominent during the locomotor cycle in this preparation. We suggest that the marked modulation of monosynaptic reflex amplitude observed in mesencephalic cats (1) arises mainly from the effects of the locomotor-drive potential in bringing the cells closer to threshold during some phases of locomotion. Specific modulation during fictive locomotion of transmission in pathways from muscle afferents, which has been demonstrated for cutaneous pathways (28), was not observed. The implications of these results for the control of locomotion are discussed briefly.

Animals↗

Direct and indirect corticospinal control of arm and hand motoneurons in the squirrel monkey (Saimiri sciureus).

Anatomic evidence suggests that direct corticomotoneuronal (CM) projections to hand motoneurons in the New World squirrel monkey (Saimiri sciureus) are weak or absent, but electrophysiological evidence is lacking. The nature of the corticospinal linkage to these motoneurons was therefore investigated first with the use of transcranial magnetic stimulation (TMS) of the motor cortex under ketamine sedation in five monkeys. TMS produced early responses in hand muscle electromyogram, but thresholds were high (compared with macaque monkey) and the onset latency was variable. Second, stimulation of the pyramidal tract (PT) was carried out with the use of chronically implanted electrodes in ketamine-sedated monkeys; this produced more robust responses that were markedly facilitated by repetitive stimulation, with little decrease in latency on the third compared with the first shock. Finally, postsynaptic potentials were recorded intracellularly from 93 arm and hand motoneurons in five monkeys under general chloralose anesthesia. After a single PT stimulus, the most common response was a small, slowly rising excitatory postsynaptic potential (EPSP), either alone (35 of 93 motoneurons) or followed by an inhibitory postsynaptic potential (39 of 93). The segmental delay of the early EPSPs was within the monosynaptic range (mean 0.85 ms); however, the rise time of these EPSPs was slow (mean 1.3 ms) and their amplitude was small (mean 0.74 mV). These values are significantly slower and smaller than EPSPs in a comparable sample of Old World macaque monkey motoneurons. The results show that CM connections do exist in the squirrel monkey but that they are weak and possibly located on the remote dendrites of the motoneurons. The findings are consistent with earlier anatomic studies. Repetitive PT stimulation produced large, late EPSPs in some motoneurons, suggesting that, in this species, there are relatively strong nonmonosynaptic pathways linking the corticospinal tract to hand motoneurons.

Animals↗

Trans-ACPD selectively inhibits excitability of hippocampal CA1 neurones.

The selective agonist of metabotropic glutamate receptors, t-ACPD (trans-1-aminocyclopentyl-1,3-dicarboxylic acid) (100-250 microM), reversibly inhibited extracellularly recorded EPSP (excitatory postsynaptic potentials) in the CA1 layer of rat hippocampus. This effect was accompanied by depression of electrical excitability of CA1 neurons as revealed by their antidromic stimulation. The excitability of CA3 neurons remained uneffected. Peculiarly, excitatory postsynaptic currents recorded in voltage clamped, internally perfused CA1 cells remained unaltered. Selective depolarization of CA1 neurons may account for the phenomena described.

Animals↗

Differential effects of elevated extracellular calcium concentrations on field potentials in dentate gyrus and CA1 of the rat hippocampal slice preparation.

The effect of a short-lasting elevation of the extracellular Ca2+ concentration (from 2 to 6 mM) on the field potentials in CA1 of the rat hippocampal slice was an increase of both the CA1 population spike (PS) and the excitatory postsynaptic potential (EPSP); this effect persisted after returning to 2 mM Ca2+ Ringer, and thus can be considered as a Ca2+-induced long-term potentiation (LTP). In the dentate gyrus (DG) a quite different effect was encountered; here the PS decreased and the EPSP increased only slightly during the perfusion with 6 mM Ca2+, and no reproducible long-term effect was induced. The results indicate that substantial differences exist in the balance between inhibitory and excitatory processes in the neural networks of the two hippocampal subregions; these differences are enhanced during perfusion with high Ca2+, which induces LTP in CA1 but not in the DG.

Animals↗

Mechanisms underlying potentiation of synaptic transmission in rat anterior cingulate cortex in vitro.

1. The properties of the excitatory synapse made by callosal inputs onto layer V and layer VI cells in the anterior cingulate cortex were studied in an in vitro slice preparation with intracellular recording. 2. In the presence of picrotoxin, the excitatory postsynaptic potential (EPSP) had two components, a fast component blocked by the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and a slow component blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV). 3. Delivery of a brief tetanus to the afferent fibres led to a long-term potentiation (LTP) of the initial slope of the monosynaptic EPSP. The LTP displayed the property of co-operativity and could be blocked by APV or by buffering intracellular calcium. 4. Pairing of low frequency presynaptic activity or weak tetanic stimulation with postsynaptic depolarization failed to potentiate the EPSP. This suggests that postsynaptic depolarization alone is unable to explain the co-operativity. 5. It is concluded that the transmitter mediating the excitatory input between callosal afferents and layer V and layer VI pyramidal neurones is glutamate. Tetanic stimulation of these afferents leads to LTP which shares many but not all the properties of LTP seen in the CA1 region of the hippocampus.

2-Amino-5-phosphonovalerate↗

Kindling-induced long-lasting changes in synaptic transmission in the basolateral amygdala.

1. Intracellular current-clamp recordings were obtained from neurons of the basolateral amygdala (BLA) in an in vitro slice preparation from control and kindled animals. Postsynaptic potentials, elicited by stimulation of the stria terminalis (ST) or lateral amygdaloid nucleus (LA), were used to investigate the role of excitatory and inhibitory amino acid transmission in kindling-induced epileptiform activity. The contributions of glutamatergic and GABAergic receptor subtypes were analyzed by use of the non-N-methyl-D-aspartate (non-NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV), and the GABAA antagonist bicuculline methiodide (BMI). 2. The synaptic waveform evoked in control neurons consisted of an excitatory postsynaptic potential (EPSP), a fast inhibitory postsynaptic potential (f-IPSP), and a slow inhibitory postsynaptic potential (s-IPSP). Stimulation of the ST or LA pathways evoked a burst-firing response in BLA neurons contralateral from the site of stimulation of kindled animals. 3. APV (50 microM) reduced, but CNQX (10 microM) completely blocked, the burst-firing response in BLA neurons from kindled animals and bicuculline-induced bursting in control neurons. 4. Kindling significantly increased the amplitude of both the slow NMDA- and the fast non-NMDA-receptor-mediated components of synaptic transmission (s- and f-EPSPs, respectively). Furthermore, the stimulus intensities required to evoke EPSPs just subthreshold for action potential generation were significantly lower in slices from kindled animals. 5. In kindled neurons no significant change was observed in the membrane input resistance and resting membrane potential or in the number of action potentials elicited in response to depolarizating current injection. 6. Kindling resulted in a pathway-specific loss of ST- and LA-evoked feedforward GABAergic synaptic transmission and of spontaneous IPSPs. In the same BLA neurons, direct GABAergic inhibition via stimulation of the LA was not affected by kindling. 7. The enhanced glutamatergic transmission was not due to disinhibition, because, in the presence of BMI (and CNQX to prevent BMI-induced bursting), the s-EPSP amplitude was still greater in kindled than in control neurons. 8. These results provide evidence that the epileptiform activity observed in BLA neurons after kindling results from an increase in excitatory NMDA- and non-NMDA-receptor-mediated glutamatergic transmission and a decrease in inhibitory gamma-aminobutyric acid (GABA)-receptor-mediated transmission; the enhanced excitatory transmission cannot be accounted for by reduced inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Long-range horizontal connections between supragranular pyramidal cells in the extrastriate visual cortex of the rat.

In this study, we examined the morphological structure and synaptic physiology of long-range axon projections among supragranular pyramidal cells in the extrastriate visual cortex of the rat. Intra- and extracellular recordings from layer II/III pyramidal cells were performed in brain slices of area 18a following extracellular stimulation of either the underlying white matter or within layer II/III. Neurons were injected with biocytin for two-dimensional reconstruction of their axon arborizations. The conduction velocity of afferent fibers (0.58 m/s) was twice as high as that of intracortical tangential fibers (0.28 m/s). Layer II/III cells were mainly di- or polysynaptically driven by afferent activation, but predominantly monosynaptically driven from intracortical stimulation sites. The afferent as well as intracortically evoked postsynaptic potentials showed a very similar time course and shape. From both stimulation sites, suprathreshold action potentials could be elicited. The current threshold for a postsynaptic response and the slope and width of excitatory postsynaptic potentials (EPSPs) increased with the distance of lateral stimulation. The morphological properties of layer II/III pyramidal cell axon collaterals closely corresponded to the electrophysiological results. Long-range intraareal axon collaterals could be followed up to 1 mm within the supragranular layers. Their length-distance distribution showed an inverse relationship to the threshold currents of EPSPs. Pyramidal cells exhibited regularly spaced patches of horizontal axon collaterals with an interpatch distance of about 250 microns. We concluded that the supragranular horizontal network in the extrastriate visual cortex of the rat is qualitatively very similar to that of cats and monkeys. However, quantitative differences exist in its spatial extent and physiological characteristics.

Animals↗

Activation of 5-HT1B receptors suppresses low but not high frequency synaptic transmission in the rat subicular cortex in vitro.

We have shown previously that activation of 5-HT1B serotonin receptors mediates suppression of the amplitude of evoked potentials in the subiculum [2]. Here we show that after application of 5-HT (10 microM), excitatory postsynaptic potentials of subicular neurons have reduced amplitudes with no change in membrane potential, input resistance and presynaptic fiber volleys. These results suggest that activation of 5-HT1B receptors reduces the release of glutamate from incoming fibers originating from CA1 pyramidal cells. In presence of 5-HT (10 microM), theta patterned stimulation still induced LTP, similar to that observed in control slices. Application of similar concentrations of 5-HT during double pulse stimulation (interval 10-15 ms) reduced the response to the first pulse (repetition interval 30 s), but the response to the second pulse of the pair was unaffected. We propose that 5-HT1B receptor activity suppresses subicular transmission at low but not at high frequencies.

Acoustic Stimulation↗

The selective activation of dorsal horn neurons by potassium stimulation of high threshold primary afferent neurons in vitro.

Intracellular recordings from neurons in the dorsal root ganglion and dorsal horn, in an in vitro spinal cord-dorsal root ganglion preparation, were used to investigate the role of large and small afferent fibers in the sensory synaptic transmission of the superficial dorsal horn. Raising the extracellular potassium concentration from 3.1 to 25-50 mM in the dorsal root ganglion compartment evoked a large amplitude depolarization and blocked action potentials in the large neurons of dorsal root ganglion, and it synaptically excited dorsal horn neurons. Excitatory postsynaptic potentials that were evoked by electrical stimulation of large myelinated fibers, but not those evoked by activation of small unmyelinated fibers, were blocked by the potassium treatment of the dorsal root. Tetrodotoxin (0.3-10 microM), when applied to the sensory neurons, abolished action potentials in large myelinated fibers but had no effect on the potassium-induced depolarization of the soma of large neurons of the dorsal root ganglion. Bath application of tetrodotoxin to the dorsal root ganglion blocked the postsynaptic potentials evoked in dorsal horn neurons by electrical stimulation of large fibers (stimulus intensity 10-20V, 0.02 ms) but failed to block postsynaptic potentials induced by electrical stimulation of slow fibers (stimulus intensity > 35 V, 0.5 ms). In addition, the tetrodotoxin failed to block the synaptic activation of dorsal horn neurons which was induced by the application of high potassium to sensory neurons. Capsaicin (10-100 microM, 10 s), applied to the sensory neurons, resulted in a prolonged synaptic activation of the dorsal horn neurons and a subsequent long lasting desensitization. During the period of capsaicin desensitization, synaptic activation of dorsal horn neurons by application of high potassium to the dorsal root ganglion and electrical stimulation of slow fibers was blocked. The opioid receptor agonist (D-Ala2, D-Leu5)-enkephalinamide (1 microM), applied to the spinal cord slice, abolished the dorsal horn neuron excitation evoked by electrical or chemical activation of slow primary afferent fibers. These findings indicate that high concentrations of K+ applied to the dorsal root ganglia selectively activate a primary afferent input to the dorsal horn, which is capsaicin sensitive and tetrodotoxin resistant.

Action Potentials↗

Suppression of long-term potentiation induction during alert wakefulness but not during 'enhanced' REM sleep after avoidance learning.

Major learning events are typically followed by a period during which the number and/or duration of rapid-eye movement sleep episodes is increased. Processes critical to memory formation are thought to take place during this interval of 'enhanced' rapid-eye movement sleep. We therefore compared the capacity for long-term potentiation during rapid-eye movement sleep and alert wakefulness after learning. Rats were chronically implanted with electrodes for stimulation of the perforant path and recording of evoked potentials and EEG in the dentate gyrus. After obtaining baseline recordings, rats were trained on a 40-trial two-way active avoidance task. Conditioned rats exhibited a two-fold increase in the mean duration of rapid-eye movement sleep episodes, as reflected by a prolongation of the hippocampal theta rhythm. There was no change in the sleep pattern of pseudoconditioned controls, which received explicitly unpaired tones and foot shocks in a yoked design. High-frequency stimulation was applied during the second, third, and fourth major rapid-eye movement sleep episodes after active avoidance training. Another group was tetanized at matching time points during alert wakefulness. After pseudoconditioning, tetanus applied during wakefulness or rapid-eye movement sleep readily induced long-term potentiation, and there was no difference between groups in the magnitude of increase for the population excitatory postsynaptic potential slope or the population spike height as measured 1 h, 24 h, and 5 days post-tetanus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of chronic stress and phenytoin on the long-term potentiation (LTP) in rat hippocampal CA1 region.

To investigate the changes of LTP in hippocampal CA1 region induced by chronic stress and the effect of phenytoin on them, thirty-two adult male Sprague-Dawley rats were randomly divided equally into four groups: control group, control-phenytoin group, stress-saline group and stress-phenytoin group. Isolated hippocampal slices of rats were used to observe the changes of long-term potentiation (LTP) in hippocampal CA1 field using electrophysiological technique. Amplitude of population spike (PS) and field excitatory postsynaptic potentials (fEPSPs) slope were used to indicate the changes of LTP. High-frequency stimulation (HFS) was applied to Schaffer collaterals of hippocampal CA3 field, and the changes of PS amplitude and fEPSPs slope in CA1 field were observed. The results showed that the LTP induction rate, the increases of PS amplitude and fEPSPs slope after HFS in control and stress-phenytoin groups were significantly greater than those in stress-saline group (P<0.05). There were no significant differences between control group and stressphenytoin group or between control and control-phenytoin groups in these indexes (P>0.05). It is suggested that chronic stress can damage the development of LTP in hippocampal CA1 field, while phenytoin can protect the LTP of stressed hippocampal slices in normal state.

Animals↗

Synaptic potentiation in the rat dentate gyrus during exploratory learning.

To investigate whether hippocampal synaptic transmission is enhanced during learning, we recorded synaptic field potentials in the dentate gyrus in response to stimulation of the perforant path in rats exploring a novel environment. Because these signals rapidly grow during brain temperature elevation, caused by any motor activity, the potentials were compared with signals sampled at similar brain temperatures after passive warming. Both the field excitatory postsynaptic potential (f-EPSP) and the population spike increased significantly early in the exploration, relative to temperature-matched control potentials. The effect decayed within 15-30 minutes. This is the first demonstration of a temperature-independent synaptic potentiation in the hippocampus during learning about the environment. The time course is similar to that of short-term potentiation.

Animals↗

Associative EPSP--spike potentiation induced by pairing orthodromic and antidromic stimulation in rat hippocampal slices.

1. Pairing low-frequency orthodromic stimulation with high-frequency antidromic conditioning of pyramidal cells in area CA1 of the rat hippocampus resulted in long-lasting potentiation of the extracellular population spike of the cells, without an accompanying increase in the extracellular excitatory postsynaptic potential (EPSP), indicating an increase in EPSP-spike (E-S) coupling, also called E-S potentiation. 2. The amplitude of the antidromically conditioned E-S potentiation took up to 60 min to reach its peak, much longer than synaptic long-term potentiation (LTP) induced by orthodromic tetanic stimulation. 3. The population spike amplitude of a control orthodromic input, which stimulated a separate set of fibres and which was inactive during the pairing, was also increased in over half the slices tested. That it can affect a silent pathway suggests that antidromically conditioned E-S potentiation is not generated locally at tetanized synapses. 4. Bath application of 50 microM D,L-2-amino-5-phosphonovaleric acid (AP5) blocked induction of antidromically conditioned E-S potentiation. After washing out the AP5, the same stimulation resulted in population spike increases. This suggests that activation of the NMDA subtype of glutamate receptor is necessary for the induction of this form of E-S potentiation. 5. Application of 10 microM picrotoxin and/or 10 microM bicuculline, which block inhibition mediated by gamma-aminobutyric acid A (GABAA) receptors, did not reduce antidromically conditioned E-S potentiation. Thus, plasticity in GABAA-mediated inhibition cannot account for the increased population spike amplitude. 6. E-S potentiation did not increase the amplitude of either extracellular or intracellular EPSPs recorded at the cell body.

2-Amino-5-phosphonovalerate↗

Mechanoafferent neurons innervating tail of Aplysia. II. Modulation by sensitizing stimulation.

The tail-withdrawal reflex of Aplysia can be sensitized by weak stimulation of a site outside the site used to test the reflex or by repeatedly stimulating the test site itself. The sensitization of tail-withdrawal responses is associated with enhanced activation of the tail motor neurons and heterosynaptic facilitation of the monosynaptic connections between the tail sensory neurons and tail motor neurons. This synaptic facilitation can occur under conditions in which neither posttetanic potentiation nor generalized changes in postsynaptic input resistance contribute to the facilitation. In addition to producing monosynaptic excitatory postsynaptic potentials (EPSPs), action potentials in tail sensory neurons often recruit longer latency polysynaptic input to the tail motor neurons during sensitization. Strong, noxious tail shock similar in intensity to that used previously for sensitization and aversive classical conditioning of other responses in Aplysia produces more heterosynaptic facilitation than does weak sensitizing stimulation. Heterosynaptic facilitation builds up progressively with multiple trials and lasts for hours. Very strong shocks to the tail can change the response characteristics of tail sensory neurons so that a prolonged, regenerative burst of spikes is elicited by a brief intracellular depolarizing pulse. This bursting response produced by sensitizing stimulation has not been described previously in Aplysia sensory neurons and can greatly amplify the synaptic input to tail motor neurons from the sensory neurons. In addition, strong shocks to the tail increase the duration and magnitude of individual sensory neuron action potentials. Sensitizing tail stimulation usually produces long-lasting depolarization of the tail motor neurons and often long-lasting hyperpolarization of the tail sensory neurons. The tail motor and sensory neurons show both increases and decreases of input resistance following sensitizing stimulation. However, the small, occasional increases in input resistance of the motor neuron are insufficient to explain the heterosynaptic facilitation produced by sensitizing stimulation. Serotonin (5-HT) application can mimic many of the effects of sensitizing tail shock, including facilitation of both tail withdrawal and the monosynaptic connections between tail sensory and motor neurons, hyperpolarizing and depolarizing responses in the tail sensory neurons, and an increase in the duration and magnitude of the sensory neuron action potential. In the nearly isolated sensory neuron soma, 5-HT usually produces a slow, decreased conductance depolarizing response, suggesting that the 5-HT-induced hyperpolarizing response see

Animals↗

Membrane properties and synaptic responses of interneurons located near the stratum lacunosum-moleculare/radiatum border of area CA1 in whole-cell recordings from rat hippocampal slices.

1. The membrane properties and synaptic inputs of interneurons, located at the stratum (s.) lacunosum-moleculare and radiatum border (L-M) of the CA1 region, were examined with the use of current-clamp whole-cell recordings in rat hippocampal slices. 2. Biocytin-labeled L-M interneurons had nonpyramidal somata and aspinous, often beaded, dendrites that arborized in s. lacunosum-moleculare and radiatum, sometimes as far as s. moleculare of the dentate gyrus. Their axon coursed and branched in s. lacunosum-moleculare and radiatum. Axon collaterals were also observed traversing the hippocampal fissure and arborizing in s. moleculare of the dentate gyrus and s. radiatum of the CA3 region. 3. Several membrane properties of interneurons were typically nonpyramidal: they had large input resistances, short-duration action potentials followed by prominent fast afterhyperpolarizations, and responded to hyperpolarizing current pulses with little membrane rectification. L-M interneurons showed significant anodal break responses, and their mean membrane time constant was 33 ms. After-depolarizations elicited by subthreshold depolarizing current pulses were larger in amplitude and decayed more slowly at depolarized than hyperpolarized membrane potentials. 4. The majority of L-M interneurons (35 of 49 cells) were silent at resting membrane potentials, whereas other displayed either spontaneous single action potentials (n = 12) or rhythmic bursts (n = 2). The rhythmic bursts were insensitive to the N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP-5; 50 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM), respectively. Both spontaneous single action potentials and burst firing were blocked by membrane hyperpolarization, suggesting that they were intrinsically rather than synaptically generated. 5. L-M interneurons responded with regular sustained firing to depolarizing current pulses at resting membrane potential. However, at more hyperpolarized membrane potentials (near -75 mV), depolarizing current pulses elicited action-potential firing with a delayed onset. This suggests that voltage-sensitive, transient outward currents may be activated in L-M interneurons from hyperpolarized membrane potentials. 6. Electrical stimulation of s. radiatum or lacunosum-moleculare elicited predominantly long-duration excitatory postsynaptic potentials (EPSPs; n = 20 cells), or both EPSPs and inhibitory postsynaptic potentials (IPSPs; n = 17 cells). In most L-M interneurons (35/37), with increasing intensities, up to two action potentials were elicited. Occasionally, larger bursts (3-5 action potentials) were observed (n = 2). 7. The multiphasic components of the synaptic responses became more evident when stimulations were repeated at different membrane potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Quantal analysis of suppressing action of baclofen on mossy fiber synapses in guinea pig hippocampus.

Baclofen, a selective agonist at the gamma-aminobutyric acidB (GABAB) receptor, has been considered to reduce the release of transmitter from nerve terminals by acting on presynaptic GABAB receptors, in addition to its postsynaptic action. The purpose of this study has been to re-examine quantitatively the action of baclofen in the hippocampus by a rigorous quantal analysis. (+/-)-Baclofen suppressed field potentials and intracellularly-recorded synaptic potentials induced in the subfield CA3 by mossy fiber stimulation in thin transverse sections of the guinea pig hippocampus. The amplitude distribution of excitatory postsynaptic potentials (EPSPs) induced monosynaptically by a granule cell could be described by the Pascal statistics. Suppression of the unitary EPSPs by baclofen (1 and 5 microM) was accompanied by decreases both in mean quantal content (m) and by mean quantal amplitude (q). The reduction in q was smaller than expected from a decrease in the input resistance of the postsynaptic neuron. It was suggested that the presynaptic and postsynaptic actions of baclofen contribute almost equally to suppression of the transmission at 1 microM, whereas the presynaptic action predominates at 5 microM.

Animals↗

Electrical membrane properties of rat subthalamic neurons in an in vitro slice preparation.

The electrical membrane properties of subthalamic (STH) neurons and their response characteristics to stimulation of the internal capsule (IC) were studied in an in vitro slice preparation. Most STH neurons recorded exhibited spontaneous repetitive firing. The input resistance of STH neurons was 146 +/- 48 M omega and showed both an anomalous and a delayed rectification when the membrane was hyperpolarized or depolarized by current injections. In neurons with the membrane potential less negative than 65 mV, depolarizing current pulses generated repetitive firing with the maximum frequency of up to 500 Hz. Two types of tetrodotoxin (TTX)-resistant cobalt-sensitive potentials, slow depolarizing potential and slow action potential, were observed in STH neurons. The slow depolarizing potential had a long duration (over 500 ms in some cases) and was able to trigger repetitive firing. The slow action potential had a duration of about 30 ms and triggered a burst of firing. The slow action potential was seen only when the neurons were hyperpolarized to more negative than 65 mV by a current injection. Electrical stimulation of IC evoked monosynaptic inhibitory postsynaptic potentials (IPSPs) in most of the neurons examined. The polarity of IPSPs was reversed in the depolarizing direction by intracellular injection of Cl-. Bath application of bicuculline markedly suppressed IPSPs and unmasked monosynaptic excitatory postsynaptic potentials (EPSPs). The EPSP was able to trigger a slow depolarization with repetitive firing or a slow action potential with burst of firing when the neuron was hyperpolarized by a continuous current injection. The results demonstrated that STH neurons in an in vitro preparation have spontaneous discharges, high input resistance, capability to generate high-frequency firing, and Ca potentials. The pattern of responses of STH neurons to synaptic inputs is dependent on their membrane potentials.

Action Potentials↗