Lateral spread of neuronal activity within the motor cortex investigated with intracellular responses to distant epicortical stimulation

Lateral spread of activity within the motor cortex was examined by means of analyses of the direct cortical responses (DCRs) and intracellular responses to distant epicortical stimulation (EPICS) using cat encéphale isolé preparations. DCRs to the EPICS at a distance of 1.5-6.5 mm consisted of initial small positive (Pd) and subsequent negative waves (Nd). The reversal of polarity in depths occurred at 400-550 microns for Pd and at 150-250 microns for Nd as well as for the initial negative wave elicited by near EPICS. Intracellular responses to distant EPICS consisted of excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP), disfacilitation (DF), and disinhibition (DI). Depth distributions of cells with EPSPs at two peaks in laminae II and V-VI, with IPSPs mainly in lamina III, and with DF or DI in laminae V-VI were the same with those by near EPICS. The inhibitory effects of distant EPICS on middle layer cells were much greater than those by near EPICS. No linear relations of the latency of EPSPs or IPSPs to the depth were seen for distant EPICS. Instead, the latency increased in proportion to the lateral distance in EPSPs at a slower rate than in IPSPs compared in superficial and middle layer cells. Several routes for lateral spread of activity were postulated. Most conspicuous are the excitatory route via horizontal axons in lamina I and the inhibitory route via laterally running axons in laminae II-III, which produce overall excitation of superficial layer cells and depression of middle and deep layer cells. Their possible role in phasic cortical arousal was discussed.     

Common response repertoire of motor cortical neurons in arousal and epicortical activation

Intracellular responses during phasic Electroencephalograph (EEG) arousal were recorded from 229 motor cortical neurons in the cat encéphale isolé preparations. Identified dominant responses were excitatory postsynaptic potentials (EPSPs) in 105 cells (E cells), inhibitory postsynaptic potentials (IPSPs) in 74 cells (I cells), disfacilitation in 48 cells (DF cells), and disinhibition in two cells (DI cells). These responses were comparable with those to near or distant epicortical stimulation (EPICS). thus, most E cells in phasic arousal were EPSP-dominant in response to near (incidence, 104/105) or distant EPICS (51/54), and only a few of the remaining were IPSP-dominant. About two-thirds of I cells were IPSP-dominant (49/74), and the remaining one-third EPSP-dominant (25/74) to near EPICS. However, most I cells became IPSP-dominant (45/49) to distant EPICS. DF and DI cells were initially EPSP- or IPSP-dominant to EPICS, but later responsive with DF in DF cells and DI in DI cells, respectively. In the interaction experiments, the initial negative wave in the direct cortical responses (DCRs) or the EPSPs of dendritic origin elicited by near EPICS and the initial positive wave in DCRs to distant EPICS were all reduced during phasic EEG arousal perhaps due to the occlusion effect. Common response repertoire in EEG arousal and epicortical activation may support the earlier proposed cascade transmission model of phasic EEG arousal, in which the spread of neuronal activities occurs vertically from the superficial to deep cortical layers as well as laterally along various layers.     

Intracortical spread of neuronal activities induced by stimulation of recurrent and thalamic afferent pathways compared with epicortical activation

In the encéphale isolé cat preparation the cerebral peduncle (CP) and the nucleus ventralis lateralis (VL) of the thalamus were stimulated. Short-latency responses recorded from precruciate cortical neurons consisted of excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP). Laminar distributions of these responses and their latencies wee viewed as the spatiotemporal pattern of spread of excitation and inhibition within the cortex in comparison with those obtained by epicortical stimulation (EPICS). In contrast with activities by EPICS spreading downwards from superficial to deep layers, CP recurrent activities spread upwards from deep to middle or superficial layers, and those by VL afferents spread from middle to both superficial and deep layers bidirectionally. These three intracortical routes shared common cell assemblies in that they received convergent EPSPs or IPSPs to various extents from different inputs. The routes for EPICS and VL inputs were overlapped particularly with abundant supply of convergence in spite of their functional difference. Relevant potentiality of the cerebral network in forming plural patterns was discussed.     

Granular cells of the mormyrid electrosensory lobe and postsynaptic control over presynaptic spike occurrence and amplitude through an electrical synapse

Primary afferent fibers from the electroreceptors of mormyrid electric fish use a latency code to signal the intensity of electrical current evoked by the fish's own electric organ discharge (EOD). The afferent fibers terminate centrally in the deep and superficial granular layers of the electrosensory lobe with morphologically mixed chemical-electrical synapses. The granular cells in these layers seem to decode afferent latency through an interaction between primary afferent input and a corollary discharge input associated with the EOD motor command. We studied the physiology of deep and superficial granular cells in a slice preparation with whole cell patch recording and electrical stimulation of afferent fibers. Afferent stimulation evoked large all-or-none electrical excitatory postsynaptic potentials (EPSPs) and large all or none GABAergic inhibitory postsynaptic potentials (IPSPs) in both superficial and deep granular cells. The amplitudes of the electrical EPSPs depended on postsynaptic membrane potential, with maximum amplitudes at membrane potentials between -65 and -110 mV. Hyperpolarization beyond this level resulted in either the abrupt disappearance of EPSPs, a step-like reduction to a smaller EPSP, or a graded reduction in EPSP amplitude. Depolarization to membrane potentials lower than that yielding a maximum caused a linear decrease in EPSP amplitude, with EPSP amplitude reaching 0 mV at potentials between -55 and -40 mV. We suggest that the dependence of EPSP size on postsynaptic membrane potential is caused by close linkage of pre- and postsynaptic membrane potentials through a high-conductance gap junction. We also suggest that this dependence may result in functionally important nonlinear interactions between synaptic inputs.     

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)     

Effects of Volleys in Cortico-spinal Tract Fibres on Ventral Spino-cerebellar Tract Cells in the Cat

Both excitation and inhibition has been found in cells of origin of the ventral spino-cerebellar tract (VSCT) to be evoked by volleys in cortico-spinal fibres. The earliest EPSPs and IPSPs had features of disynaptically evoked postsynaptic potentials; these were, however, found only in a small proportion of cells and polysynaptic EPSPs and IPSPs were dominating. Postsynaptic potentials evoked in VSCT cells from primary afferents were effectively facilitated by cortico-spinal volleys. The cortico-spinal effects on VSCT cells may thus well be mediated by the same interneurones which mediate their excitation or inhibition from the periphery and which could evoke similar postsynaptic potentials in motoneurones. Generally all the observations are in keeping with the hypothesis (Lundberg 1971) that VSCT cells monitor transmission through interneurones interposed in various reflex paths to motoneurones.     

Vestibulo-ocular reflex from the posterior canal nerve to extraocular motoneurons in the cat

Summary In the anesthetized cat, the posterior canal nerve (PCN) was stimulated by electric pulses and synaptic responses were recorded intracellularly in the three antagonistic pairs of extraocular motoneurons. Pure reciprocal effects were obtained in the motoneurons innervating the antagonistic pair of ipsilateral oblique muscles and the antagonistic pair of contralateral vertical rectus muscles. These responses consisted of low threshold disynaptic excitatory postsynaptic potentials (EPSPs) in either the contralateral superior oblique (c-SO) (trochlear) or contralateral inferior rectus (c-IR) motoneurons and of disynaptic inhibitory postsynaptic potentials (IPSPs) in either the ipsilateral inferior oblique (i-IO) or ipsilateral superior rectus (i-SR) motoneurons. In addition, disynaptic IPSPs were also found in (i-SO) motoneurons. Mixtures of low threshold (dior trisynaptic) EPSPs and IPSPs were found in all other extraocular motoneurons except for the contralateral lateral rectus (c-LR) motoneurons. These results may afford a basis for the characteristic eye movements induced by vertical canal nerve stimulation.     

Synaptic potentials evoked in spiny neurons in rat neostriatal grafts by cortical and thalamic stimulation.

1. Fetal rat striatal primordia were implanted into the neostriatum of adult rats 2 days after kainic acid lesion. Two to 6 mo after transplantation, in vivo intracellular recording and staining were performed to study the responses of spiny neurons in the grafts to the cortical and thalamic stimuli. The physiological characteristics and synaptic responses of 27 cells recorded in the grafts were compared with a sample of 23 neurons recorded from the surrounding host neostriatum in the same animals. Nineteen of the graft neurons and 19 of the host neurons were identified as spiny neurons by intracellular staining with biocytin. The responses of the remaining neurons were the same as those of identified spiny cells. 2. The spontaneous synaptically driven membrane potential shifts and long-lasting responses to afferent stimulation that are characteristic of neostriatal cells in normal animals were greatly reduced or absent in graft neurons. Presumably this reflects the reduction in synaptic input to the grafts and the lack of convergence of inputs from diverse sources. 3. Short-latency synaptic responses to cortical and thalamic stimulation were present and could consist of either excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs). The IPSPs were accompanied by a membrane conductance increase, and their reversal potentials could be altered by injection of chloride ions. Several minutes after impaling the cell, the IPSPs gradually disappeared, and the same stimuli could then evoke EPSPs. The disappearance of the IPSPs was independent of the presence of chloride in the electrodes. Most of the EPSP responses appeared to be monosynaptic but occurred at longer latencies than those seen in host neurons of the same type. 4. In cells not exhibiting IPSPs, or after the IPSP responses disappeared, cortical or thalamic stimulation could evoke slow depolarizing potentials and bursts of action potentials. These could not be evoked by current injection. They could be prevented or delayed by an exaggerated action potential after hyperpolarization that developed in neurons maintained in a depolarized state for several seconds, but could not be prevented by passage of hyperpolarizing current from the recording electrode. 5. The input resistance of graft spiny neurons was higher than that of the host cells, and time constants were longer. Both of these properties appeared to be due to the absence of the strong inward rectification that is usually present at resting membrane potentials in neostriatal neurons.     

Electrophysiological properties and input-output organization of callosal neurons in cat association cortex

Intracellular recordings from association cortical areas 5 and 7 were performed in cats under barbiturate or ketamine-xylazine anesthesia to investigate the activities of different classes of neurons involved in callosal pathways, which were electrophysiologically characterized by depolarizing current steps. Excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), and/or antidromic responses were elicited by stimulating homotopic sites in the contralateral cortical areas. Differential features of EPSPs related to latencies, amplitudes, and slopes were detected in closely located (50 microm or less) neurons recorded in succession along the same electrode track. In contrast to synchronous thalamocortical volleys that excited most neurons within a cortical column, stimuli applied to homotopic sites in the contralateral cortex activated neurons at restricted cortical depths. Median latencies of callosally evoked EPSPs were 1.5 to 4 ms in various cortical cell-classes. Fast-rhythmic-bursting neurons displayed EPSPs whose amplitudes were threefold larger, and latencies two- or threefold shorter, than those found in the three other cellular classes. Converging callosal and thalamic inputs were recorded in the same cortical neuron. EPSPs or IPSPs were elicited by stimulating foci spaced by <1 mm in the contralateral cortex. In the overwhelming majority of neurons, latencies of antidromic responses were between 1.2 and 3.1 ms; however, some callosal neurons had much longer latencies, 相似文献   

Laminar distribution of neuronal membrane properties in neocortex of normal and reeler mouse.

1. Reeler is an autosomal recessive mutation of mice that alters neuronal migration during development, yielding a general inversion of the laminae in the neocortex. We recorded in vitro from slices of normal and reeler neocortex to study the influence of neuron position and shape on membrane properties and synaptic responses. 2. The intrinsic firing patterns, action-potential shapes, resting membrane potentials, input resistances, and evoked excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) did not differ between reelers and controls when data were grouped. 3. The depth distribution of intrinsic firing patterns was inverted in the reeler: intrinsically bursting (IB) neurons were found only in layer 5 in the normal mouse, but they were found exclusively in supragranular layers of the reeler cortex. 4. The spatial distribution of synaptic responses in the reeler was also inverted: very prominent IPSPs were characteristic of upper layer neurons in the normal mouse, but in the reeler similar inhibitory responses were observed predominantly in deep infragranular layers. 5. Dye injections in reeler pyramidal neurons revealed atypical morphologies, including distorted apical dendrites and cell inversion. 6. The data imply that cortical neurons develop the membrane and synaptic properties appropriate to their function, despite being malformed and mispositioned.     

Effects on peroneal motoneurons of cutaneous afferents activated by mechanical or electrical stimulations

The postsynaptic potentials elicited in peroneal motoneurons by either mechanical stimulation of cutaneous areas innervated by the superficial peroneal nerve (SP) or repetitive electrical stimulation of SP were compared in anesthetized cats. After denervation of the foot sparing only the territory of SP terminal branches, reproducible mechanical stimulations were applied by pressure on the plantar surface of the toes via a plastic disk attached to a servo-length device, causing a mild compression of toes. This stimulus evoked small but consistent postsynaptic potentials in every peroneal motoneuron. Weak stimuli elicited only excitatory postsynaptic potentials (EPSPs), whereas increase in stimulation strength allowed distinction of three patterns of response. In about one half of the sample, mechanical stimulation or trains of 20/s electric pulses at strengths up to six times the threshold of the most excitable fibers in the nerve evoked only EPSPs. Responses to electrical stimulation appeared with 3-7 ms central latencies, suggesting oligosynaptic pathways. In another, smaller fraction of the sample, inhibitory postsynaptic potentials (IPSPs) appeared with an increase of stimulation strength, and the last fraction showed a mixed pattern of excitation and inhibition. In 24 of 32 motoneurons where electrical and mechanical effects could be compared, the responses were similar, and in 6 others, they changed from pure excitation on mechanical stimulation to mixed on electrical stimulation. With both kinds of stimulation, stronger stimulations were required to evoke inhibitory postsynaptic potentials (IPSPs), which appeared at longer central latencies than EPSPs, indicating longer interneuronal pathways. The similarity of responses to mechanical and electrical stimulation in a majority of peroneal motoneurons suggests that the effects of commonly used electrical stimulation are good predictors of the responses of peroneal motoneurons to natural skin stimulation. The different types of responses to cutaneous afferents from SP territory reflect a complex connectivity allowing modulations of cutaneous reflex responses in various postures and gaits.     

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.     

Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons.

1. The interaction between inhibitory interneurons and cortical pyramidal neurons was studied by use of computer simulations to test whether inhibitory interneurons could assist in phase-locking postsynaptic cells. Two models were used: a simplified model, which included only 3 membrane channels, and a detailed 11-channel model. 2. The 11-channel model included most of the ion channels known to be present in neocortical pyramidal neurons as well as calcium diffusion and other membrane mechanisms. The kinetics for the channels were obtained from voltage-clamp studies in a variety of preparations. The parameters were then adjusted to produce repetitive bursting similar to that seen in some cortical pyramidal cells entrained during visual stimulation. 3. Phase-locking to a train of inhibitory postsynaptic potentials (IPSPs) located on or near the soma was observed in the 3-channel model cell subjected to random synaptic bombardment. In the 11-channel model, phase-locking due to multiple IPSPs was compared with phase-locking due to multiple excitatory postsynaptic potentials (EPSPs). Phase-locking began to occur when 20% of the IPSPs (20/100) or 40% of the EPSPs (4,000/10,000) were synchronized. The exact percentages differed with different 11-channel models, but either EPSPs or IPSPs would generally produce entrainment with approximately 40% synchronization. Thus 40 inhibitory boutons had an effect equivalent to 4,000 excitatory boutons in producing phase-locking. 4. Phase-locking with IPSPs in these models was possible because the IPSPs could cause either an increase or a decrease in firing rate over a limited range. The IPSPs served a modulatory role, increasing the rate of firing in some cases and decreasing it in others, depending on the state of the cell. 5. We examined frequency entrainment by IPSPs. In the 3-channel model, frequency entrainment of a postsynaptic cell was observed with a rapid train of strong (20-100 nS), brief, compound IPSPs. A 40-Hz compound IPSP train of 60 nS entrained cells having initial firing rates between 32 and 47 Hz. Below this range, cells could be partially entrained. Above the range, entrainment would fail. Frequency entrainment in the 3-channel model generally occurred on the first cycle after onset of the IPSPs. 6. Phase-locking and frequency entrainment were less robust in the 11-channel model. This was partly because bursts rather than individual spikes were being entrained. A 40-Hz, 90-nS compound IPSP train entrained a model cell upward from 34 Hz. Downward frequency entrainment also occurred.(ABSTRACT TRUNCATED AT 400 WORDS)     

D-baclofen does not antagonize the actions of L-baclofen on rat neocortical neurons in vitro

The ability of D-baclofen to antagonize the actions of L-baclofen on rat neocortical neurons was investigated. Intracellular recordings were made from neurons in cortical layers 2 and 3 in an in vitro slice preparation. Baclofen stereoisomers were applied at known concentrations in the superfusion medium. At a concentration of 3 microM, L-baclofen produced approximately 70% depressions of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) that were evoked by stimulation of superficial cortical layers. L-baclofen also hyperpolarized neocortical neurons. These hyperpolarizations were accompanied by decreases in neuronal input resistance and in direct excitability. We have shown previously that these latter effects are secondary to the action of baclofen to increase the potassium conductance of neocortical neurons. D-baclofen, at concentrations of 1-100 microM, did not antagonize depressions by L-baclofen of EPSPs and IPSPs nor the action of L-baclofen to increase the potassium conductance of neocortical neurons. At concentrations of 50-100 microM, D-baclofen produced 20-30% effects when applied alone, thus suggesting that these concentrations of D-baclofen produced a significant degree of receptor occupancy. Our results demonstrate that D-baclofen is not an antagonist or high affinity partial agonist at the receptors through which baclofen exerts its effects on single neurons in the rat neocortex.     

Horizontal spread of synchronized activity in neocortex and its control by GABA-mediated inhibition

1. Suppression of GABAA receptor-mediated inhibition disrupts the neural activity of neocortex and can lead to synchronized discharges that mimic those of partial epilepsy. We have studied the role of GABAA-mediated inhibition in controlling the synchronization and horizontal (tangential) spread of cortical activity. 2. Slices of rat SmI were maintained in vitro and focally stimulated in layer VI while recording with a horizontal array of extracellular electrodes. Inhibition was slightly suppressed by adding low concentrations of the GABAA antagonists bicuculline or bicuculline methiodide to the bathing medium. Under control conditions neural activity was narrowly confined to a vertical strip of cortex. The horizontal spread of activity expanded about twofold in the presence of antagonist concentrations (less than or equal to 0.5 microM) that were expected to suppress GABAA function by no more than 10-20%. 3. At antagonist concentrations between 0.4 and 1.0 microM, evoked epileptiform activity appeared. These threshold-dose epileptiform events showed wide variations in size and duration (even at the same recording site), very variable distances of horizontal propagation, specific sites of propagation failure, reversals of propagation direction, and directional asymmetries in their probability of propagation. This contrasts with activity observed previously (Ref. 9) in high bicuculline concentrations (greater than or equal to 10 microM): large, stereotyped events that propagate reliably without decrement or reflection. 4. Intracellular recordings were obtained from pyramidal neurons in layers II/III in the presence of less than or equal to 1 microM bicuculline. Inhibitory postsynaptic potentials (IPSPs) were observed during both primary evoked responses and propagating epileptiform events and were often comparable in size and duration to those in untreated cortex. Epileptiform field potentials were always correlated with synaptic activity in single cells, but the pattern and type of PSPs varied with the form of the field potentials. Large amplitude epileptiform events coincided with an overwhelming inhibition of upper layer neurons. 5. We conclude that 1) the horizontal spread of normal cortical activity is strongly constrained by GABAA-mediated IPSPs, 2) a relatively small reduction in the efficacy of inhibition leads to a large increase in the spread of excitation, 3) initiation and propagation of synchronized epileptiform activity can occur even in the presence of robust cortical inhibition, and 4) the character of epileptiform activity is strongly affected by the influences of inhibition.     

Nature of inhibitory postsynaptic activity in developing relay cells of the lateral geniculate nucleus

Using intracellular recordings in an isolated (in vitro) brain stem preparation, we examined the inhibitory postsynaptic responses of developing neurons in the dorsal lateral geniculate nucleus (LGN) of the rat. As early as postnatal day (P) 1-2, 31% of all excitatory postsynaptic (EPSP) activity evoked by electrical stimulation of the optic tract was followed by inhibitory postsynaptic potentials (IPSPs). By P5, 98% of all retinally evoked EPSPs were followed by IPSP activity. During the first postnatal week, IPSPs were mediated largely by GABA(A) receptors. Additional GABA(B)-mediated IPSPs emerged at P3-4 but were not prevalent until after the first postnatal week. Experiments involving the separate stimulation of each optic nerve indicated that developing LGN cells were binocularly innervated. At P11-14, it was common to evoke EPSP/IPSP pairs by stimulating either the contralateral or ipsilateral optic nerve. During the third postnatal week, binocular excitatory responses were encountered far less frequently. However, a number of cells still maintained a binocular inhibitory response. These results provide insight about the ontogeny and nature of postsynaptic inhibitory activity in the LGN during the period of retinogeniculate axon segregation.     

Increased pyramidal excitability and NMDA conductance can explain posttraumatic epileptogenesis without disinhibition: a model.

Partially isolated cortical islands prepared in vivo become epileptogenic within weeks of the injury. In this model of chronic epileptogenesis, recordings from cortical slices cut through the injured area and maintained in vitro often show evoked, long- and variable-latency multiphasic epileptiform field potentials that also can occur spontaneously. These events are initiated in layer V and are synchronous with polyphasic long-duration excitatory and inhibitory potentials (currents) in neurons that may last several hundred milliseconds. Stimuli that are significantly above threshold for triggering these epileptiform events evoke only a single large excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). We investigated the physiological basis of these events using simulations of a layer V network consisting of 500 compartmental model neurons, including 400 principal (excitatory) and 100 inhibitory cells. Epileptiform events occurred in response to a stimulus when sufficient N-methyl-D-aspartate (NMDA) conductance was activated by feedback excitatory activity among pyramidal cells. In control simulations, this activity was prevented by the rapid development of IPSPs. One manipulation that could give rise to epileptogenesis was an increase in the threshold of inhibitory interneurons. However, previous experimental data from layer V pyramidal neurons of these chronic epileptogenic lesions indicate: upregulation, rather than downregulation, of inhibition; alterations in the intrinsic properties of pyramidal cells that would tend to make them more excitable; and sprouting of their intracortical axons and increased numbers of presumed synaptic contacts, which would increase recurrent EPSPs from one cell onto another. Consistent with this, we found that increasing the excitability of pyramidal cells and the strength of NMDA conductances, in the face of either unaltered or increased inhibition, resulted in generation of epileptiform activity that had characteristics similar to those of the experimental data. Thus epileptogenesis such as occurs after chronic cortical injury can result from alterations of intrinsic membrane properties of pyramidal neurons together with enhanced NMDA synaptic conductances.     

Mormyromast electroreceptor organs and their afferent fibers in mormyrid fish. II. Intra-axonal recordings show initial stages of central processing

1. Physiologically and morphologically identified primary afferent fibers from mormyromast electroreceptor organs were recorded intracellularly. The fiber recordings were made from the nerve root of the posterior lateral line nerve, where the fibers enter the brain, and from the electrosensory lateral line lobe (ELL), near the central terminals of the fibers. 2. The intracellular recordings reveal a variety of potentials, synaptic and nonsynaptic, in addition to the large orthodromic action potentials from the periphery. The goal of the present study was to describe and interpret these various potentials in mormyromast afferent fibers as a first step in understanding the processing of electrosensory information in ELL. 3. Three types of synaptic potentials were recorded inside mormyromast afferent fibers: 1) electric organ corollary discharge (EOCD) excitatory postsynaptic potentials (EPSPs), driven by the motor command that elicits the electric organ discharge (EOD); 2) EPSPs evoked by electrosensory stimulation of electroreceptors in the skin near the electroreceptor from which the recorded fiber originates or by direct stimulation of an electrosensory nerve; and 3) inhibitory postsynaptic potentials (IPSPs) evoked by electrosensory stimulation of more distant electroreceptors. These synaptic potentials can be attributed to synaptic input to postsynaptic cells in ELL that is observed inside the afferent fibers because of electrical synapses between the fibers and the postsynaptic cells. 4. The peripherally evoked EPSPs could frequently be shown to be unitary. The unitary EPSPs were identical to the orthodromic spikes in originating from a single electroreceptor, in threshold, and in latency shift with increasing stimulus intensity. These similarities suggest that the unitary EPSPs are electrotonic EPSPs caused by impulses in other mormyromast afferent fibers that terminate on some of the same postsynaptic cells as the recorded fiber. The peripherally evoked IPSPs had a longer latency than the EPSPs or orthodromic spikes, requiring the presence of an inhibitory interneuron. 5. The peripherally evoked EPSPs, both unitary and nonunitary, show absolute refractory periods of 3-8 ms, followed by relative refractory periods of approximately 8 ms, when tested with two identical stimuli to a nerve. These refractory periods are interpreted as because of refractoriness in the fine preterminal branches of the axonal arbor. 6. A depolarizing afterpotential is commonly associated with the orthodromic spike and probably results from the successful propagation of the spike into the entire terminal arbor. The depolarizing afterpotential has a refractory period that is similar to that of the peripherally evoked EPSPs and that is also interpreted as refractoriness in the fine preterminal branches.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Widely integrative properties of layer 5 pyramidal cells support a role for processing of extralaminar synaptic inputs in rat neocortex

We have compared the length, strength, conduction velocity and divergence of horizontal connections onto layers 2/3 and 5 neurons in slices of rat primary somatosensory neocortex. Slices were cut along laminar borders to eliminate most vertical connections, and excitatory postsynaptic potentials (EPSPs) were recorded from pyramidal cells in adjacent uncut tissue. When electric stimuli were delivered within the same layer as the recorded cell, EPSPs could be evoked up to 2000 microm away for both layers 2/3 and 5 pyramids. Estimates of horizontal axonal conduction velocities ( approximately 0.4 m/s) and the thresholds for activation also did not differ between layers. However, layers 2/3 cells rarely responded to stimuli delivered to isolated deeper layers, while layer 5 neurons were often excited by horizontal inputs from isolated layers 2/3 and 4.