Auditory thalamocortical transmission is reliable and temporally precise

We have used the auditory thalamocortical slice to characterize thalamocortical transmission in primary auditory cortex (ACx) of the juvenile mouse. "Minimal" stimulation was used to activate medial geniculate neurons during whole cell recordings from regular-spiking (RS cells; mostly pyramidal) and fast-spiking (FS, putative inhibitory) neurons in ACx layers 3 and 4. Excitatory postsynaptic potentials (EPSPs) were considered monosynaptic (thalamocortical) if they met three criteria: low onset latency variability (jitter), little change in latency with increased stimulus intensity, and little change in latency during a high-frequency tetanus. Thalamocortical EPSPs were reliable (probability of postsynaptic responses to stimulation was approximately 1.0) as well as temporally precise (low jitter). Both RS and FS neurons received thalamocortical input, but EPSPs in FS cells had faster rise times, shorter latencies to peak amplitude, and shorter durations than EPSPs in RS cells. Thalamocortical EPSPs depressed during repetitive stimulation at rates (2-300 Hz) consistent with thalamic spike rates in vivo, but at stimulation rates > or = 40 Hz, EPSPs also summed to activate N-methyl-D-aspartate receptors and trigger long-lasting polysynaptic activity. We conclude that thalamic inputs to excitatory and inhibitory neurons in ACx activate reliable and temporally precise monosynaptic EPSPs that in vivo may contribute to the precise timing of acoustic-evoked responses.     

Induction of long-term potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex.

1. Intracellular recording was made from layer II-III cells in slice preparations of kitten (30-40 days old) visual cortex. Low-frequency (0.1 Hz) stimulation of white matter (WM) usually evoked an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). The postsynaptic potentials (PSPs) showed strong dependence on stimulus frequency. Early component of EPSP and IPSP evoked by weak stimulation both decreased monotonically at frequencies greater than 0.5-1 Hz. Strong stimulation similarly depressed the early EPSP at higher frequencies (greater than 2 Hz) and replaced the IPSP with a late EPSP, which had a maximum amplitude in the stimulus frequency range of 2-5 Hz. 2. Very weak WM stimulation sometimes evoked EPSPs in isolation from IPSPs. The falling phase of the EPSP revealed voltage dependence characteristic to the responses mediated by N-methyl-D-aspartate (NMDA) receptors and was depressed by application of an NMDA antagonist DL-2-amino-5-phosphonovalerate (APV), whereas the rising phase of the EPSP was insensitive to APV. 3. The early EPSPs followed by IPSPs were insensitive to APV but were replaced with a slow depolarizing potential by application of a non-NMDA antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX), indicating that the early EPSP is mediated by non-NMDA receptors. The slow depolarization was mediated by NMDA receptors because it was depressed by membrane hyperpolarization or addition of APV. 4. The late EPSP evoked by higher-frequency stimulation was abolished by APV, indicating that it is mediated by NMDA receptors, which are located either on the recorded cell or on presynaptic cells to the recorded cells. 5. Long-term potentiation (LTP) of EPSPs was examined in cells perfused with solutions containing 1 microM bicuculline methiodide (BIM), a gamma-aminobutyric acid (GABA) antagonist. WM was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes were tested by low-frequency (0.1 Hz) stimulation of WM. 6. LTP of early EPSPs occurred in more than one-half of the cells (8/13) after strong conditioning stimulation. The rising slope of the EPSP was increased 1.6 times on average. 7. To test involvement of NMDA receptors in the induction of LTP in the early EPSP, the effect of conditioning stimulation was studied in a solution containing 100 microM APV, which was sufficient to block completely synaptic transmission mediated by NMDA receptors. LTP occurred in the same frequency and magnitude as in control solution.     

Properties of primary sensory (lemniscal) synapses in the ventrobasal thalamus and the relay of high-frequency sensory inputs

The main role of the thalamus is to relay sensory inputs to the neocortex. In the primary somatosensory thalamus (ventrobasal thalamus), sensory inputs deliver tactile information through the medial lemniscus tract. The transmission of sensory information through this pathway is affected by behavioral state. For instance, the relay of high-frequency somatosensory inputs through the thalamus is suppressed during anesthesia or quiescent states but allowed during behaviorally activated states. This change may be due to the effects of modulators on the efficacy of lemniscal synapses. Here I show that lemniscal synapses of adult rodents studied in vitro produce large amplitude-highly secure unitary excitatory postsynaptic potentials (EPSPs), which depress in response to repetitive stimulation at frequencies >2 Hz. Acetylcholine and norepinephrine, which are important thalamic modulators, have no effect on the efficacy of lemniscal EPSPs but reduce evoked inhibitory postsynaptic potentials and corticothalamic EPSPs. Although acetylcholine and norepinephrine do not affect lemniscal synapses, the postsynaptic depolarization they produce on thalamocortical neurons serves to warrant the relay of lemniscal inputs at high-frequency rates by bringing the depressed lemniscal EPSPs close to firing threshold. In conclusion, acetylcholine and norepinephrine released during activated states selectively enhance sensory transmission through the lemniscal pathway by depolarizing thalamocortical neurons and simultaneously depressing the other afferent pathways.     

Two distinct types of corticothalamic EPSPs and their contribution to short-term synaptic plasticity

The lateral posterior nucleus (LPN) is innervated by two different morphological types of cortical terminals that originate from cortical layers V and VI. Here we describe two distinct types of excitatory postsynaptic potentials (EPSPs) that were recorded in the LPN after stimulation of corticothalamic fibers. These types of EPSPs differed in amplitude, latency, rise time, and response to increasing levels of stimulus intensity. The most frequently encountered EPSP, type I, displayed a longer latency and slower rise time than the less frequently encountered type II EPSP. Type I EPSPs also showed a graded increase in amplitude with increasing levels of stimulation, whereas type II EPSPs showed an all-or-none response. In response to repetitive stimulation (0.5-20 Hz), type I EPSPs displayed frequency-dependent facilitation, whereas type II EPSPs displayed frequency-dependent depression. Further details of these distinct forms of short-term synaptic plasticity were explored using paired-pulse stimuli. Pharmacology experiments revealed that both N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors are involved in corticothalamic synaptic transmission in the LPN and contribute to both synaptic facilitation and depression. Taken together with the results of our previous anatomical studies, these results suggest that type I EPSPs arise from stimulation of layer VI afferents, whereas type II EPSPs arise from stimulation of layer V inputs. Moreover, type I and II EPSPs in the LPN may be functionally similar to corticogeniculate and retinogeniculate EPSPs, respectively.     

Stimulus-evoked modulation of sensorimotor pyramidal neuron EPSPs

Sensory cortical neurons display substantial receptive field dynamics during and after persistent sensory drive. Because a cell's response properties are determined by the inputs it receives, receptive field dynamics are likely to involve changes in the relative efficacy of different inputs to the cell. To test this hypothesis, we have investigated if brief repetitive stimulus drive in vitro alters the efficacy of two types of corticocortical inputs to layer V pyramidal cells. Specifically, we have used whole cell recordings to measure the effect of repetitive electrical stimulation at the layer VI/white matter (WM) border on the synaptic response of layer V pyramidal cells to corticocortical input evoked by electrical stimulation of layer I or layer II/III and emulated by local application of glutamate. Repetitive stimulation (10 Hz for 3 s) at the layer VI/WM border transiently potentiated excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of layer II/III by 97 +/- 12% (mean +/- SE). The recovery of EPSP amplitude to its preconditioning value was well-described by a single-term decaying exponential with a time constant of 7.2 s. The same layer VI/WM conditioning train that evoked layer II/III EPSP potentiation frequently caused an attenuation of layer I EPSPs. Similarly, subthreshold postsynaptic responses to local glutamate application in layers II/III and I were potentiated and attenuated, respectively, by the conditioning stimulus. Potentiation and attenuation could be evoked in the same cell by repositioning the glutamate puffer pipette in the appropriate layer. The conditioning stimulus that led to the transient modification of upper layer EPSP efficacy also evoked a slow depolarization in glial cells. The membrane potential of glial cells recovered with a time course similar to the dissipation of the potentiation effect, suggesting that stimulus-evoked changes in extracellular potassium (ECK) play a role in layer II/III EPSP potentiation. Consistent with this proposal, increasing the bath concentration of ECK caused a substantial increase of layer II/III EPSP amplitude. EPSP potentiation was sensitive to postsynaptic membrane potential and, more importantly, was significantly weaker for synaptic currents than for synaptic potentials, suggesting that it involves the recruitment of a postsynaptic voltage-dependent mechanism. Two observations suggest that layer II/III EPSP potentiation may involve the recruitment of postsynaptic sodium channels: EPSP potentiation was strongly reduced by intracellular application of N-(2,6-dimethyl-phenylcarbamoylmethyl) triethylammonium bromide (QX-314) and responses to local glutamate application were potentiated by high ECK in the presence of cadmium but not in the presence of tetrodotoxin. The results demonstrate a novel way in which brief periods of repetitive stimulus drive are accompanied by rapid, transient, and specific alterations in the functional connectivity and information processing characteristics of sensorimotor cortex.     

Excitatory postsynaptic potentials in rat neocortical neurons in vitro. III. Effects of a quinoxalinedione non-NMDA receptor antagonist

1. Intracellular microelectrodes were used to obtain recordings from neurons in layer II/III of rat frontal cortex. A bipolar electrode positioned in layer IV of the neocortex was used to evoke postsynaptic potentials. Graded series of stimulation were employed to selectively activate different classes of postsynaptic responses. The sensitivity of postsynaptic potentials and iontophoretically applied neurotransmitters to the non-N-methyl-D-asparate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was examined. 2. As reported previously, low-intensity electrical stimulation of cortical layer IV evoked short-latency early excitatory postsynaptic potentials (eEPSPs) in layer II/III neurons. CNQX reversibly antagonized eEPSPs in a dose-dependent manner. Stimulation at intensities just subthreshold for activation of inhibitory postsynaptic potentials (IPSPs) produced long-latency (10 to 40-ms) EPSPs (late EPSPs or 1EPSPs). CNQX was effective in blocking 1EPSPs. 3. With the use of stimulus intensities at or just below threshold for evoking an action potential, complex synaptic potentials consisting of EPSP-IPSP sequences were observed. Both early, Cl(-)-dependent and late, K(+)-dependent IPSPs were reduced by CNQX. This effect was reversible on washing. This disinhibition could lead to enhanced excitability in the presence of CNQX. 4. Iontophoretic application of quisqualate produced a membrane depolarization with superimposed action potentials, whereas NMDA depolarized the membrane potential and evoked bursts of action potentials. At concentrations up to 5 microM, CNQX selectively antagonized quisqualate responses. NMDA responses were reduced by 10 microM CNQX. D-Serine (0.5-2 mM), an agonist at the glycine regulatory site on the NMDA receptor, reversed the CNQX depression of NMDA responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency dependent corticofugal excitation of principal cells in the cat's dorsal lateral geniculate nucleus

Excitatory postsynaptic potentials (EPSPs) were evoked in principal cells of the cat's dorsal lateral geniculate nucleus by electrical stimulation of cortico-geniculate fibres. The EPSPs had a pronounced frequency sensitivity. They were barely detectable at stimulation frequencies below 3 Hz but increased dramatically in size at higher frequencies. At 30-50 Hz their amplitude typically exceeded that of EPSPs from optic tract fibres. A prominent EPSP potentiation was also obtained with pair pulse stimulation. The findings are discussed in relation to the hypothesis that the cortico-geniculate system serves as a variable gain regulator for the visual input to the cortex.     

Role of GABAB receptor-mediated inhibition in reciprocal interareal pathways of rat visual cortex

In neocortex, synaptic inhibition is mediated by gamma-aminobutyric acid-A (GABAA) and GABAB receptors. By using intracellular and patch-clamp recordings in slices of rat visual cortex we studied the balance of excitation and inhibition in different intracortical pathways. The study was focused on the strength of fast GABAA- and slow GABAB-mediated inhibition in interareal forward and feedback connections between area 17 and the secondary, latero-medial visual area (LM). Our results demonstrate that in most layer 2/3 neurons forward inputs elicited excitatory postsynaptic potentials (EPSPs) that were followed by fast GABAA- and slow GABAB-mediated hyperpolarizing inhibitory postsynaptic potentials (IPSPs). These responses resembled those elicited by horizontal connections within area 17 and those evoked by stimulation of the layer 6/white matter border. In contrast, in the feedback pathway hyperpolarizing fast and slow IPSPs were rare. However weak fast and slow IPSPs were unmasked by bath application of GABAB receptor antagonists. Because in the feedback pathway disynaptic fast and slow IPSPs were rare, polysynaptic EPSPs were more frequent than in forward, horizontal, and interlaminar circuits and were activated over a broader stimulus range. In addition, in the feedback pathway large-amplitude polysynaptic EPSPs were longer lasting and showed a late component whose onset coincided with that of slow IPSPs. In the forward pathway these late EPSPs were only seen with stimulus intensities that were below the activation threshold of slow IPSPs. Unlike strong forward inputs, feedback stimuli of a wide range of intensities increased the rate of ongoing neuronal firing. Thus, when forward and feedback inputs are simultaneously active, feedback inputs may provide late polysynaptic excitation that can offset slow IPSPs evoked by forward inputs and in turn may promote recurrent excitation through local intracolumnar circuits. This may provide a mechanism by which feedback inputs from higher cortical areas can amplify afferent signals in lower areas.     

Frequency dependent corticofugal excitation of principal cells in the cat's dorsal lateral geniculate nucleus

Summary Excitatory postsynaptic potentials (EPSPs) were evoked in principal cells of the cat's dorsal lateral geniculate nucleus by electrical stimulation of cortico-geniculate fibres. The EPSPs had a pronounced frequency sensitivity. They were barely detectable at stimulation frequencies below 3 Hz but increased dramatically in size at higher frequencies. At 30–50 Hz their amplitude typically exceeded that of EPSPs from optic tract fibres. A prominent EPSP potentiation was also obtained with pair pulse stimulation. The findings are discussed in relation to the hypothesis that the cortico-geniculate system serves as a variable gain regulator for the visual input to the cortex.     

Long-term adaptation in lobster motor neurons and compensation of transmitter release by synergistic inputs

Earlier studies with crayfish have shown that chronic increases in neural activity, by electrical stimulation, cause a long-lasting reduction in the amount of transmitter released at low stimulus frequencies or at the beginning of a stimulus train. When such chronic stimulation is applied to phasic extensor motor neurons of the lobster abdomen, a similar change in transmitter release is apparent, as indicated by a decrease in excitatory postsynaptic potential (EPSP) size at 0.1 Hz. However, the EPSPs from unstimulated axons which innervate the same target muscle from a different nerve increase in size. Thus, activity-dependent reduction in transmitter release at one set of synapses appears to be compensated for by increased synaptic efficacy from less active synergistic inputs. The mechanism of such compensation is not known.     

Depression of postsynaptic potentials by high-frequency stimulation in embryonic motoneurons grown in spinal cord slice cultures.

1. In embryonic cocultures of spinal cord, dorsal root ganglia, and muscle, excitatory postsynaptic potentials (EPSPs) were recorded in motoneurons during focal electrical stimulation of the dorsal root ganglia or the spinal cord. 2. EPSPs were depressed in amplitude at high-frequency stimulation relative to a control frequency of 0.5 Hz by 47 and 75% at 5 and 10 Hz, respectively. This was true for composite EPSPs and unitary EPSPs. 3. The depression showed a wide range of variability between individual experiments. The degree of depression at 5 Hz was negatively correlated to the rate of spontaneous excitatory input the motoneurons received. There was no correlation to the soma size, the average amplitude of the EPSPs, the rheobase, or the input resistance of the motoneurons. 4. An increase in latency of EPSPs was observed concomitant with or preceding the synaptic depression in most experiments. Total transmission failures, which were absent at low-frequency stimulation, appeared during depression. 5. Large incremental steps in amplitude could be seen during depression, suggesting that several release sites were switched off and on together. 6. Decreasing the extracellular calcium concentration from 5 to 1 mM led to a decrease in the frequency sensitivity of the synaptic efficacy and to a decrease of the EPSP amplitude and latency. 7. Measurements of the antidromic conduction of action potentials evoked in the axons and recorded in the somata of dorsal root ganglion cells revealed an increase in latency and the appearance of conduction failures at stimulation frequencies of 1-10 Hz. The frequency modulation of conduction was decreased in 1 mM compared with 5 mM external calcium. 8. Together these findings suggest that conduction failures in the presynaptic axons contribute to the synaptic depression of EPSPs in embryonic motoneurons.     

Effects of a dorsal column lesion on temporal processing within the somatosensory system of primates

A dorsal column (DC) lesion has lasting effects on behavioral tasks that require temporal processing of tactile information (e.g., frequency and duration discrimination). The present experiments describe physiological correlates of these deficits in temporal discrimination. Compound action potentials evoked by electrocutaneous stimulation were recorded from the major white matter subdivisions of the spinal cord in anesthetized monkeys, and relationships between stimulation frequency and evoked potential (EP) amplitude were determined for the ascending pathways. At 10 pulses per second (Hz) EPs recorded in the lateral spinal columns were attenuated slightly (by 15% or less, relative to 1.5 Hz), whereas potentials recorded from the DCs were not attenuated. The attenuation increased with stimulation frequencies up to 50 Hz, reaching 80% for the anterolateral column and 38% for the dorsolateral column, but only 15% for the DC. Epidural EPs were recorded, before and after interruption of the contralateral DC, from awake animals with electrodes chronically implanted over primary somatosensory cortex (SI). Following the lesion, EP responses to 1.5-Hz stimulation were 46% of preoperative responses to the same stimulus. At 10 Hz, EP amplitudes were attenuated even more, to 27% of the preoperative amplitude at 1.5 Hz. Principal components analysis was employed to quantify alterations in EP conformation and stimulus frequency was varied from 1.5 to 10 Hz, before and after a DC lesion. Interruption of the DC resulted in a significant decrease in the information provided by the EP about changes in stimulus frequency. EPs were also recorded from different locations along the anterior-posterior dimension of the hindlimb region of SI in lightly anesthetized animals. Principal components analysis revealed that there was less information present in the EP about changes in stimulus frequency (1.5–10 Hz) at all recording locations in animals with a DC lesion, compared with the cortex of normal animals. The DC lesion significantly decreased the amplitude of cortical EPs evoked by repetitive stimulation. At 10 Hz the EP was nearly buried in noise, consistent with behavioral deficits in discrimination of the duration of 10 Hz stimulation following interruption of the DC. Also, significantly less information was present in the cortical EPs about changes in stimulus frequency in the absence of intact DCs, which is consistent with deficits in frequency discrimination. This reduction could be explained in part by a lesser capacity of spinal pathways in the lateral column to follow repetitive stimulation above 10 Hz. However, more rostral manifestations of a DC lesion, at either the thalamus or the cortex, are likely to contribute to the reduced capacity of animals with DC lesions to make temporal discriminations.     

Synaptic mechanisms of inspiratory off-switching evoked by pontine pneumotaxic stimulation in cats

To elucidate synaptic mechanisms and the involvement of N-methyl-D-aspartate (NMDA) receptors in inspiratory off-switching (IOS) evoked by the stimulation of the nucleus parabrachialis medialis (NPBM), excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were recorded from bulbar augmenting inspiratory (aug-I) and postinspiratory (PI) neurons in vagotomized cats. Stimulation of NPBM produced either transient inhibition or premature termination of inspiration (reversible or irreversible IOS), depending on the stimulus intensity. Each neuron displayed four-phasic postsynaptic responses during the reversible IOS, i.e. Phase 1 EPSPs, Phase 2 IPSPs, Phase 3 EPSPs and Phase 4 IPSPs in aug-I neurons, and Phase 1 plus 2 EPSPs, Phase 3 IPSPs and Phase 4 EPSPs in PI neurons. During the irreversible IOS, Phase 4 responses were replaced by sustained hyperpolarization in aug-I neurons and decrementing depolarization in PI neurons. Blockade of NMDA receptors by dizocilpine (0.3 mg kg(-1) i.v.) selectively increased Phase 4 potentials in both types of neurons and decreased the thresholds for evoking the irreversible IOS. The NPBM-induced responses had a pattern and time-course similar to those induced by vagal stimulation. The present results suggest that pneumotaxic and vagal inputs converge on the common IOS circuit, and the effectiveness of both inputs is modulated by NMDA receptors.     

Intracellular analysis of trigeminal motoneuron rhythmical activity during stimulation of pontomedullary reticular formation in anesthetized guinea pig

1. The effects of repetitive stimulation of the nucleus pontis caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation on jaw opener and closer motoneurons were examined. The PnC-Gi was stimulated at 75 Hz at current intensities less than 90 microA. 2. Rhythmically occurring, long-duration, depolarizing membrane potentials in jaw opener motoneurons [excitatory masticatory drive potential (E-MDP)] and long-duration hyperpolarizing membrane potentials [inhibitory masticatory drive potentials (I-MDP)] in jaw closer motoneurons were evoked by 40-Hz repetitive masticatory cortex stimulation. These potentials were completely suppressed by PnC-Gi stimulation. PnC-Gi stimulation also suppressed the short-duration, stimulus-locked depolarizations [excitatory postsynaptic potentials (EPSPs)] in jaw opener motoneurons and short-duration, stimulus-locked hyperpolarizations [inhibitory postsynaptic potentials (IPSPs)] in jaw closer motoneurons, evoked by the same repetitive cortical stimulation. 3. Short pulse train (3 pulses; 500 Hz) stimulation of the masticatory area of the cortex in the absence of rhythmical jaw movements activated the short-latency paucisynaptic corticotrigeminal pathways and evoked short-duration EPSPs and IPSPs in jaw opener and closer motoneurons, respectively. The same PnC-Gi stimulation that completely suppressed rhythmical MDPs, and stimulus-locked PSPs evoked by repetitive stimulation to the masticatory area of the cortex, produced an average reduction in PSP amplitude of 22 and 17% in jaw closer and opener motoneurons, respectively. 4. PnC-Gi stimulation produced minimal effects on the amplitude of the antidromic digastric field potential or on the intracellularly recorded antidromic digastric action potential. Moreover, PnC-Gi stimulation had little effect on jaw opener or jaw closer motoneuron membrane resting potentials in the absence of rhythmical jaw movements (RJMs). PnC-Gi stimulation produced variable effects on conductance pulses elicited in jaw opener and closer motoneurons in the absence of RJMs. 5. These results indicate that the powerful suppression of cortically evoked MDPs in opener and closer motoneurons during PnC-Gi stimulation is most likely not a result of postsynaptic inhibition of trigeminal motoneurons. It is proposed that this suppression is a result of suppression of activity in neurons responsible for masticatory rhythm generation.     

Reticulospinal excitation and inhibition of neck motoneurons

Summary Responses of neck motoneurons to electrical stimulation of the pontomedullary reticular formation were recorded intracellularly in cerebellectomized cats anesthetized with chloralose. Stimulation of nucleus reticularis (n.r.) ventralis and the dorsal part of n.r. gigantocellularis evoked short latency, monosynaptic inhibitory postsynaptic potentials (IPSPs) in the majority of motoneurons supplying the ipsilateral splenius, biventer cervicis and complexus muscles and in 25% of motoneurons projecting in the ipsilateral spinal accessory nerve. Monosynaptic IPSPs were also evoked by stimulating the medial longitudinal fasciculus (MLF) but lesion and collision experiments indicated that these IPSPs were independent of those evoked by reticular stimulation. Monosynaptic IPSPs were also occasionally observed following stimulation of the contralateral reticular formation, especially of the dorsal part of n.r. gigantocellularis.Monosynaptic excitatory postsynaptic potentials (EPSPs) were evoked in all classes of neck motoneurons studied by stimulation of n.r. pontis caudalis, gigantocellularis and ventralis. Each reticular nucleus appeared to contribute to this excitation. The excitation was bilateral but large monosynaptic EPSPs were most often seen in motoneurons ipsilateral to the stimulus site. Data indicated that pontine EPSPs were mediated by ventromedial reticulospinal fibers while medullary EPSPs were mediated by ventrolateral reticulospinal fibers. Neck motoneurons thus receive at least three distinct direct reticulospinal inputs, two excitatory and one inhibitory.Supported in part by grants NSF BMS 75-00487 and NIH NS 02619Recipient of N.I.H. Fellowship 1 F32 NS 05027     

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

Summary 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. 5. The functional significance of the excitatory inputs from the PN and the NRTP to the DN is discussed in relation to the motor control mechanisms of the cerebellum.     

Excitatory and inhibitory effects on human spinal motoneurones from magnetic brain stimulation

Stimulation of baboon motor cortex causes in the motoneurones (MNs) of intrinsic hand muscles monosynaptic excitatory postsynaptic potentials (EPSPs) and a disynaptic inhibitory postsynaptic potential (IPSP). These phenomena have been investigated in human MNs by applying pulsed magnetic stimuli over the scalp at random times during the tonic discharge of single hand muscle motor units (MUs). Post-stimulus time histograms (PSTHs) demonstrated an increased firing probability at between 25 and 35 ms. This major firing peak showed a multimodal form with interpeak intervals of 1.4-1.8 ms. When MUs were not fired by the stimulus, they were nevertheless inhibited from firing spontaneously. There are thus short latency excitatory and inhibitory cortical inputs to human MNs.     

Synaptic organization of the cerebello-thalamo-cerebral pathway in the cat. I. Projection of individual cerebellar nuclei to single pyramidal tract neurons in areas 4 and 6

The neural connections of the dentate (DN) and the interpositus (IN) nuclei to the motor cortex and area 6 were investigated by recording intracellular postsynaptic potentials from fast and slow pyramidal tract neurons (PTNs) in the anesthetized cat. Localized stimulation of DN and IN produced di- or polysynaptic EPSPs in fast and slow PTNs in the "forelimb area" of the motor cortex and area 6. The effects of stimulation of the two cerebellar projections were essentially the same, although some regional difference of their relative strength was noted. In these cortical areas, the majority of fast and slow PTNs received convergent inputs from both DN and IN. By examining the interaction of DN- and IN-evoked EPSPs, spatial facilitation and occlusion at the level of the thalamus were demonstrated. Therefore, it was concluded that at least a portion of the convergence of the dentate and the interpositus inputs occurred at the level of the ventrolateral nucleus of the thalamus.     

Frequency dependent inhibition of the nicotinic transmission by serotonin in vesical pelvic ganglia of the rabbit

Intracellular recordings were made from neurons in rabbit vesical pelvic ganglia (VPG), in vitro. Increasing the frequency of preganglionic-nerve stimulations from 0.1-1 Hz to 10-20 Hz facilitated fast excitatory postsynaptic potentials (EPSPs), resulting in a generation of action potentials. Acetylcholine-induced response was not altered during the facilitation of the fast EPSP. Serotonin blocked action potentials elicited by preganglionic-nerve stimulations at 0.1 Hz, while it caused no blockade at 10 Hz. Serotonin may potentiate the feature of high-pass filter in transmission of VPG. Immunohistochemical study demonstrated serotonin-like varicose terminals in rabbit VPG.     

Frequency dependence of synaptic transmission in nucleus of the solitary tract in vitro

Afferent fibers from visceral sensory receptors enter the medulla oblongata, form the solitary tract, and synapse with neurons in the nucleus of the solitary tract. In the present study longitudinal slices were prepared from guinea pig medulla in order to examine the properties of transmission at these synapses in vitro. Synaptic responses to selective stimulation of solitary tract fibers were recorded intracellularly from neurons in an area, close to the obex and immediately medial and lateral to the tract, where arterial baroreceptor fibers are known to terminate. The amplitude of maximally evoked postsynaptic potentials (PSPs) in solitary tract neurons was strongly dependent on stimulus frequency. On increasing frequency from 0.5 to 20 Hz, a PSP depression of 80% was reached in 4-8 s. The mean depression was 35% at 5 Hz and 60% at 10 Hz. Sufficient local connections were retained in vitro that solitary tract stimulation evoked disynaptic inhibitory potentials and long latency, possibly polysynaptic, excitatory potentials in some neurons. The possibility that frequency-dependent changes in the efficacy of these local synaptic circuits contributed to PSP depression was examined. The role of postsynaptic inhibition in synaptic depression was tested by examining the frequency dependence of PSPs at membrane potentials close to the reversal of their excitatory component. The resulting hyperpolarizing PSPs were also depressed suggesting that a facilitation of postsynaptic inhibition at high frequency does not underlie the depression. The contribution of depression in multisynaptic excitatory pathways to PSP depression was assessed by exclusion. At low stimulus intensities, excitatory synaptic events with no long latency components were evoked. These events exhibited a similar frequency dependence to that of maximal PSPs. These results suggest that mechanisms operating at synapses made by solitary tract fibers are responsible for the frequency dependence of PSPs recorded in solitary tract neurons. Such mechanisms might contribute to the adaptation of some cardiovascular reflexes initiated by baroreceptors.