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.     

Excitatory and inhibitory postsynaptic potentials in alpha-motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region

We tested the hypothesis that stimulation of the mesencephalic locomotor region (MLR) activates polysynaptic pathways that project to lumbar spinal motoneurons and are involved in the initiation of locomotion. Fictive locomotion was produced by MLR stimulation, and intracellular records of evoked postsynaptic potentials (PSPs) in alpha-motoneurons were computer analyzed. Stimulation of sites in the MLR that were maximally effective for the initiation of locomotion produced excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in all the motoneurons examined. The amplitudes of the PSPs increased as locomotion commenced. The EPSPs were largest during the depolarized phase of the step cycle, and in 17 of our 22 cells the EPSP was replaced by an IPSP of slightly longer latency during the hyperpolarized phase. The mean latency of the EPSPs measured from the stimulus artifact produced by stimulation of the MLR was 5.1 ms (3.0-7.0 ms). In all cases, the IPSP occurred 0.6 ms or more after the onset of the EPSP in the same cell. Later PSPs were sometimes observed as well. The effects of constant current injection on the membrane potential oscillations associated with fictive locomotion (locomotor drive potentials) were examined. The results showed that the amplitudes of the locomotor drive potentials (LDPs) could be affected by depolarizing and hyperpolarizing current injection. The data is consistent with the LDP having a predominant inhibitory component, which is more readily altered by current injection than is the excitatory component. The effect of constant current injections on the MLR-evoked PSPs was also examined, and it was observed that both EPSPs and IPSPs could be affected by the injected currents. The EPSPs increased in amplitude with constant hyperpolarizing current injection, and this fact rules out the possibility that the EPSP is actually a reversed IPSP. The IPSP was decreased in amplitude by hyperpolarizing current injection. Combined stimulation of the MLR and the ipsilateral high-threshold muscle or cutaneous afferents produced facilitation of both short- and long-latency MLR-evoked PSPs, suggesting that the two pathways share common interneurons. The possibility that the long-latency PSPs are produced by rapid oscillation in the locomotor central pattern generator is discussed. We concluded that MLR stimulation that evokes fictive locomotion produces both excitation and inhibition of spinal motoneurons. Spinal interneuronal systems are implicated and may be those involved in the initiation and control of locomotion. The probable relay sites for the descending pathway from the MLR to motoneurons are discussed.     

In vivo recording of postsynaptic potentials and low threshold spikes in W cells of the cat's lateral geniculate nucleus

Summary We obtained good intracellular recording from 5 W cells in the C-laminae of the cat's lateral geniculate nucleus. The recordings were made from an anesthetized and paralyzed in vivo preparation. We found a consistent pattern for the postsynaptic potentials evoked from activation of the optic chiasm: first was an IPSP followed by an EPSP. This is very different from the pattern seen in X and Y cells, for which an EPSP always appears first and is then followed by an IPSP. We interpret the pattern for W cells as follows. The initial IPSP is disynaptic; this involves retinogeniculate conduction over very fast Y axons and a relay through an interneuron. The EPSP is monosynaptic, reflecting retinogeniculate conduction over very slow W axons. A possible implication for this is that activity over the Y pathway may generally inhibit geniculate W cells before these W cells can be excited by their retinal afferents. Finally, we elicited from each of these W cells voltage-dependent, low threshold spikes, which are very similar to those displayed by X and Y cells. These spikes can interrupt normal retinogeniculate transmission, and they are prevented by maintaining relatively depolarized membrane potentials.     

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.     

Quantitative studies of intracellular postsynaptic potentials in the lateral geniculate nucleus of the cat with respect to optic tract stimulus response latencies

Summary LGN cells were intracellularly recorded with glass micropipettes. Electrical stimuli of different amplitude and frequency were applied to the optic tract close to the optic chiasm. The cells were classified according to stimulus response latencies of action potentials as belonging to class I (1.0–1.6 msec) or class II (1.7–3.0 msec).Class I EPSPs had shorter latencies (1.0–1.5 msec), durations (4–12 msec), rise times to peak (0.5–1.4 msec), and decay times (3.0–8.5 msec); the synaptic transmission time was on the average 0.41 msec. Class II EPSPs (1.6–2.6 msec latency) had longer durations (10–30 msec), rise times (1.6–3.7 msec), and decay times (9.0–25 msec); the synaptic transmission time was on the average 0.67 msec.With repetitive stimulation the EPSPs of latency class I revealed almost no stimulus frequency dependence between 1 and 120 Hz, while class II EPSPs decreased in amplitude between 30 and 70% with increasing frequency. Comparable temporal summation of excitation occurred in cells of both latency classes. Negative serial correlation coefficients of first order were found for consecutive EPSP amplitudes of all cells recorded for sufficient periods of time.The IPSPs were subdivided into two groups according to their optic tract response latency. Group 1 IPSPs had shorter latencies (2.0–2.6 msec), durations (15–50 msec), and times from the onset to maximal hyperpolarization (2.4–4.2 msec) than group 2 IPSPs (3.0–4.8 msec latency, 40–100 msec duration, 2.7–7.5 msec time from onset to extremum).The group 2 IPSPs decreased in amplitude by about 90% when the stimulus frequency was increased from 1 to 50 Hz, while the group 1 IPSPs displayed a comparable decrease in the frequency range between 50 and 120 Hz. Effective temporal summation was found in group 2 IPSPs in the frequency range below 70 Hz, and in group 1 IPSPs at stimulus frequencies between 70 and 120 Hz.The EPSP peak latencies and the latencies to the minimum of IPSPs proved to be invariant with respect to PSP amplitude and stimulus frequency in individual cells. The latencies to the extrema of EPSPs and IPSPs as well as the amplitude values were symmetrically distributed.     

Postsynaptic potentials mediated by excitatory and inhibitory amino acids in interneurons of stratum pyramidale of the CA1 region of rat hippocampal slices in vitro.

1. Because interneurons of stratum pyramidale partly mediate the feed-forward inhibition of pyramidal cells, intracellular postsynaptic potentials (PSPs) evoked by activation of afferent fibers were examined in 32 nonpyramidal cells of stratum pyramidale of the CA1 region of rat hippocampal slices. 2. Electrical stimulation of stratum radiatum at the CA1-CA3 border elicited, in interneurons, PSPs that were composed of four components: a fast excitatory postsynaptic potential (EPSP), an early inhibitory postsynaptic potential (IPSPA), a late IPSPB, and in some cells a delayed, slower EPSP. These synaptic potentials summated and elicited single action potentials in 57% of cells (17/30) and burst of action potentials (2-10) in the remaining 43%. 3. The fast EPSP was observed in all cells, and the mean stimulation intensity at its threshold was 53.4 microA. Its amplitude increased with membrane hyperpolarization, and it was associated with a 45.4% decrease in cellular input resistance. The fast EPSP always elicited an action potential at short latencies (3.6-6.4 ms poststimulation). It was reversibly reduced by 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX), a blocker of non-N-methyl-D-aspartate (non-NMDA) excitatory amino acid receptors. 4. The IPSPA was observed in 28/32 cells, and the mean intensity of stimulation was 57.6 microA at its threshold. The mean latency of its peak amplitude was 17.4 ms. The mean equilibrium potential (Erev) was -72.8 mV, and it was associated with a 38.9% decrease in cellular input resistance. IPSPA was blocked by the GABAA antagonist bicuculline. 5. The IPSPB was seen in 29/32 cells, and the mean intensity of stimulation at its threshold was 80.3 microA. Its latency to peak was 130.6 ms, its Erev was -107.6 mV, and it was associated with a small (7.6%) decrease in cellular input resistance. IPSPB was blocked by the GABAB antagonist phaclofen. 6. In 11/32 cells a slower EPSP was also observed. Its mean latency to peak was 53.3 ms, and the mean intensity of stimulation at its threshold was 89.4 microA. In two cells its amplitude decreased with membrane hyperpolarization, and its was associated with a 6.8% increase in cellular input resistance. In 8 of 13 cells showing burst responses, this slow EPSP was present. 7. Both EPSPs and IPSPs were sensitive to repetitive stimulation. The amplitude of the fast EPSP was potentiated during paired-pulse stimulation at interstimulus intervals between 30 and 200 ms and occasionally depressed at intervals of 10-20 ms.(ABSTRACT TRUNCATED AT 400 WORDS)     

Intracellular and extracellular in vivo recording of different response modes for relay cells of the cat's lateral geniculate nucleus

Summary Prior studies of thalamic neurons have demonstrated that they exhibit at least two response modes: a relay mode and a burst mode. During the relay mode, sensory information is faithfully relayed to cortex; during the burst mode, which is caused by a voltagedependent Ca²⁺ conductance, this relay of sensory information is interrupted. We began in vivo studies of these response modes in neurons from the lateral geniculate nucleus of anesthetized, paralyzed cats. Each of the 9 X and 10 Y cells we recorded intracellularly displayed voltage-dependent, low threshold spikes that were presumably the Ca²⁺ spikes described from in vitro recording. These spikes were triangular in waveform and typically had 2–7 fast action potentials (interspike intervals of 1.2–4 ms) riding its crest. Furthermore, the cell's membrane had to be hyperpolarized to de-inactivate the low threshold spike before a depolarization could then activate it. We could activate these low threshold spikes in Y cells from EPSPs, whether spontaneous or evoked from activation of the optic chiasm. However, in only one of the X cells could we activate low threshold spikes from chiasm shock; in the remainder, we could activate low threshold spikes only via depolarizing current pulses, possibly because the EPSPs of these X cells were too small to activate these spikes. We also used extracellular recording to study spontaneous activity and responses to chiasm shock from 114 geniculate neurons and, as a control, 57 optic tract axons. We concentrated on periods of bursty responsiveness signifying the burst mode. We define a burst as 2–7 action potentials with interspike intervals <= 4 ms, and the bursts are separated by > 100 ms; from our intracellular recording, we know that such bursts signify low threshold spikes. We found that, during extracellular recording, 20 of the 39 X cells and each of the 75 Y cells displayed evidence of the burst response mode, although burst periods were rare in X cells. Electrical activation of the optic chiasm greatly enhanced the burstiness of Y cells for periods of 500 ms or more. We also electrically stimulated the parabrachial region of the midbrain, which provides a mostly cholinergic innervation to the lateral geniculate nucleus. Although parabrachial activation by itself had no detectable effect on Y cell response modes, prior parabrachial activation prevented the enhanced burstiness caused by chiasm stimulation. This parabrachial effect lasted for roughly 500 ms after stimulation. Neither chiasm nor parabrachial stimulation, singly or in combination, had a noticeable effect on the bursting activity of X cells. Finally, none of the extracellularly recorded retinogeniculate axons (23 X and 34 Y) showed any evidence of burst responses. This supports the conclusion that the burst responses we found for geniculate neurons represent an emergent property of the lateral geniculate nucleus, and this burstiness reflects an interruption of retinogeniculate transmission. We conclude that geniculate X and Y cells do indeed show evidence during extracellular recording of maintaining two very different response modes and that, under our recording conditions, Y cells are much more prone to burst activity than are X cells.     

Neuronal pathways from low-threshold hindlimb cutaneous afferents to motoneurons innervating trunk muscles in low-spinal cats

Postsynaptic potentials (PSPs) evoked in motoneurons innervating the back and abdominal muscles in the lumbar part of the body by stimulating hindlimb cutaneous afferents were investigated in unanesthetized decerebate and spinal cats. Various types of PSP: pure excitatory postsynaptic potential (EPSP), pure inhibitory postsynaptic potential (IPSP), and mixed PSP (i.e., EPSP followed by IPSP, EPSP/IPSP; and IPSP followed by EPSP, IPSP/EPSP) were observed. The weak stimulation at 2 times threshold (2T) produced predominantly the EPSP, while at 5T the incidence of IPSP or EPSP followed by IPSP was increased. In about 20-50% of the various groups of motoneurons, PSPs evoked by ipsi- and contralateral nerves were qualitatively and quantitatively similar. For the other motoneurons, PSPs evoked by ipsi- and contralateral nerves were markedly different with respect to magnitude and/or polarity. These findings suggest that, within each motoneuron pool, some neurons act to increase stiffness of the trunk or to move vertically in response to an increased activity of cutaneous afferents, while the other motoneurons act to produce lateral bending of the trunk.     

Intracellular correlates of spatial memory acquisition in hippocampal slices: long-term disinhibition of CA1 pyramidal cells

Despite many advances in our understanding of synaptic models of memory such as long-term potentiation and depression, cellular mechanisms that correlate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic responses of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisition. Schaffer collateral stimulation evoked complex postsynaptic potentials (PSP) consisting of the excitatory and inhibitory postsynaptic potentials (EPSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and correlation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyses revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced IPSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related facilitation as compared with the swim and na?ve controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no learning-specific synaptic changes. There were no WM training-specific modifications of other intrinsic membrane properties. These data suggest that long-term disinhibition in a subset of CA1 PCs may facilitate cell discharges that represent and record the spatial location of a hidden platform in a Morris WM.     

A differential synaptic input to the motor nuclei of triceps surae from the caudal and lateral cutaneous sural nerves

1. Postsynaptic potentials (PSPs) were recorded in 115 triceps surae motoneurons of 10 chloralose-anesthetized adult cats (spinal cord intact), upon electrical stimulation of the caudal and lateral cutaneous sural nerve branches (CCS and LCS, respectively). 2. With twice threshold (2T) stimulation of CCS, excitatory PSPs (EPSPs) were the predominant effect in 95% of all medial gastrocnemius (MG) motoneurons tested (min. central latency 1.5 ms; mean 2.4 ms). In only a few MG cells was the EPSP followed by an inhibitory postsynaptic potential (IPSP) and in only one cell was an IPSP the sole effect. Increasing the stimulus intensity to 5T tended to enhance both the later EPSP and IPSP components, with less change in the amplitude or latency of the earliest EPSPs. 3. In lateral gastrocnemius (LG) and soleus (SOL) motoneurons, 2T CCS stimulation led to either inhibition or no potential change in the majority of cells tested: EPSPs were the predominant effect in only 15 and 30% of LG and SOL cells, respectively (min. central latency 2.5 ms; mean 3.0 ms) and rarely occurred without subsequent inhibition. Again, increasing the stimulus intensity to 5T had more of an effect on later rather than earlier PSP components. 4. A predominance of depolarization in MG motoneurons but not in SOL motoneurons is in agreement with previous findings that CCS excitation is more powerful in "fast type" triceps surae motoneurons. However, the strong predominance of hyperpolarizing effects of CCS stimulation in the present LG population is evidence that such an organization does not transcend triceps surae motor nuclei as a whole. 5. Postsynaptic effects of LCS stimulation at 2T were frequently weak or absent but increasing the stimulus intensity to 5T produced predominant inhibition in 71% of all triceps surae motoneurons studied (n = 107). Of the few cells which did receive excitation from this nerve, most were MG, a few were SOL, and none were LG. These EPSPs occurred more frequently at 5T than at lower stimulation strengths. 6. The results indicate that excitation produced by electrical stimulation of the ipsilateral CCS nerve occurs preferentially in the MG portion of triceps surae and with the shortest central latencies. Effects of LCS stimulation are largely inhibitory throughout the motor nuclei comprising triceps surae but even here, the presence of excitation occurs more frequently in MG. A comparison of these results with those in other reports is discussed.     

Synaptic responses of guinea pig cingulate cortical neurons in vitro.

1. Intracellular recordings were made from layer V/VI neurons of the guinea pig anterior cingulate cortex to investigate postsynaptic potentials (PSPs) evoked by electrical stimulation of the subcortical white matter (forceps minor). 2. Four distinct types of PSPs were recorded (at the resting potential) under normal physiological conditions; 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic potentials (EPSPs) were followed by bicuculline- or picrotoxin-sensitive depolarizing or hyperpolarizing inhibitory postsynaptic potentials (IPSPs), which were further followed by phaclofen-sensitive, long-lasting hyperpolarizing postsynaptic potentials (LPSPs). The average times-to-peak for the EPSP, depolarizing and hyperpolarizing IPSPs, and LPSP were 10, 22, 28, and 146 ms, respectively. 3. In the presence of CNQX and bicuculline, high-intensity electrical stimulation elicited a longer lasting EPSP with a time-to-peak of 21 ms. The amplitude and duration of the EPSP decreased with membrane hyperpolarization and increased with membrane depolarization. The EPSP was reversibly abolished by D,L-2-amino-5-phosphonovaleric acid (D,L-APV). 4. The bicuculline- or picrotoxin-sensitive depolarizing and hyperpolarizing IPSPs and the phaclofen-sensitive LPSP were markedly suppressed by CNQX, suggesting that glutamate (Glu) and/or aspartate nerve terminals project to GABAergic interneurons, and that the GABAergic interneurons are activated mainly by non-N-methyl-D-aspartate (non-NMDA) receptors. 5. In the presence of picrotoxin, the average reversal potential for the compound EPSP was 0 mV, which was similar to that (-6 mV) for the Glu-induced depolarization. In a solution containing D,L-APV at low concentrations, the average reversal potentials for the depolarizing and hyperpolarizing IPSPs and for the early and late components of the gamma-aminobutyric acid (GABA)-induced responses were -62, -72, -70, and -61 mV, respectively. Thus the value for the depolarizing IPSP was similar to that for the late response to GABA, whereas the value for the hyperpolarizing IPSP was almost the same as that for the early response to GABA. The average reversal potential of -90 mV for the LPSP was similar to -93 mV for the baclofen-induced hyperpolarization and to -94 mV for the spike afterhyperpolarization. 6. Application of phaclofen decreased the interspike interval of the spontaneous firing and reversed the increase in the interspike interval after subcortical stimulation. This result indicates that, even in a slice preparation, the anterior cingulate neurons are under tonic inhibitory control exerted by spontaneously active GABAergic interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Postsynaptic potentials in the hypoglossal motoneurons set up by hypoglossal nerve stimulation.

In nembutalized cats intracellular potentials were recorded from hypoglossal motoneurons innervating either protruder or retractor muscles of the tonge (protruder and retractor motoneurons: P-Mns and R-Mns). Responses to stimulation of the hypoglossal nerve were explored and found to consist of an antidromic spike followed by an afterhyperpolarization (AHP) and a postsynaptic potential (PSP). When hypoglossal nerve stimulation was made with an intensity three times as large as the threshold for the hypoglossal motor fibers, the PSPs became evident under blockage of soma-dendritic invasion of the antidromic spike. In most of P-Mns or R-Mns, the PSPs were IPSPs, independent of the side of peripheral stimulation. The latencies were about 12 msec. Even when the cell membrane was hyperpolarized by injecting a hyperpolarizing current of up to 16 nA, the reversal point of the IPSP was difficult to find. In a small fraction of hypoglossal motoneurons the PSPs to hypoglossal nerve stimulation were EPSPs with latencies of 10 to 12 msec.     

Rubrospinal Effects on Ventral Spinocerebellar Tract Neurones

Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms.     

Postsynaptic potentials evoked in ventrobasal thalamus neurones by natural sensory stimuli

Intracellular recordings were made in the ventrobasal thalamus of rats anaesthetised with urethane. Postsynaptic responses were evoked by stimulation of the peripheral receptive field with an air jet of 10 ms duration. The postsynaptic response typically consisted of an excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequence with one or more evoked action potentials. Injection of hyperpolarizing current pulses appeared to increase the EPSP amplitude, whereas depolarising current pulses caused a reduction in EPSP amplitude. These changes in EPSP amplitude were however obscured by the presence of IPSPs and a slow potential similar to a low-threshold Ca2+ spike (LTS).     

Rubrospinal effects on ventral spinocerebellar tract neurones.

Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms.     

Supraspinal facilitation of cutaneous polysynaptic EPSPs in cat medial gastrocnemius motoneurons

Summary We examined the characteristics of postsynaptic potentials (PSPs) produced in antidromically-identified medial gastrocnemius (MG) -motoneurons by electrical stimulation of low threshold (< 3×T) distal limb cutaneous afferents in the sural (SUR) nerve in adult cats anesthetized with -chloralose, together with the effects on SUR PSPs of supraspinal conditioning stimulation of the contralateral red nucleus (RN) and pyramidal tract (PT). In the majority of MG motoneurons, SUR afferents with electrical thresholds < 1.5×T produced early excitatory synaptic potentials (EPSPs) with minimum central latency of about 2.0 ms, suggesting activation of a trisynaptic segmental pathway with two interposed interneurons. Such early EPSPs were often detectable with stimuli < 1.2×T, as determined by recording the compound action potential in the sciatic nerve and from the first appearance of the N₁ wave of the cord dorsum potential. Inhibitory synaptic potentials (IPSPs) were regularly produced by SUR volleys of only slightly greater strength (often as low as 1.3×T) and these had minimum central latencies of about 3.0 ms (about 1.0 ms longer than the earliest EPSPs), suggesting a three interneuron central pathway.Repetitive stimulation of RN and PT regularly produced facilitation of both EPSP and IPSP components in the SUR response, suggesting that these supraspinal systems directly or indirectly excite some of the same interneurons that convey the SUR effects to MG motoneurons. When using very low strength SUR stimuli, PT conditioning produced relatively pure facilitation of the SUR EPSPs but with larger SUR volleys, PT clearly facilitated both EPSPs and IPSPs. RN conditioning produced more parallel facilitation of SUR EPSPs and IPSPs. Supraspinal control of the polysynaptic pathway producing SUR EPSPs is of particular interest because of earlier evidence that this pathway is differentially distributed to motoneurons of fast twitch versus slow twitch MG motor units.Supported by USPHS Postdoctoral Fellowship 1F32NS 06131Supported by Muscular Dystrophy Society of America Post-doctoral FellowshipSupported by USPHS Postdoctoral Fellowship 1F32NS 05677     

Synaptic responses of neurons controlling the parotid and von Ebner salivary glands in rats to stimulation of the solitary nucleus and tract

Salivary secretion results from reflex stimulation of autonomic neurons via afferent sensory information relayed to neurons in the rostral nucleus of the solitary tract (rNST), which synapse with autonomic neurons of the salivatory nuclei. We investigated the synaptic properties of the afferent sensory connection to neurons in the inferior salivatory nucleus (ISN) controlling the parotid and von Ebner salivary glands. Mean synaptic latency recorded from parotid gland neurons was significantly shorter than von Ebner gland neurons. Superfusion of GABA and glycine resulted in a concentration-dependent membrane hyperpolarization. Use of glutamate receptor antagonists indicated that both AMPA and N-methyl-D-aspartate (NMDA) receptors are involved in the evoked excitatory postsynaptic potentials (EPSPs). Inhibitory postsynaptic potential (IPSP) amplitude increased with higher intensity ST stimulation. Addition of the glycine antagonist strychnine did not affect the amplitude of the IPSPs significantly. The GABA(A) receptor antagonist, bicuculline (BMI) or mixture of strychnine and BMI abolished the IPSPs in all neurons. IPSP latency was longer than EPSP latency, suggesting that more than one synapse is involved in the inhibitory pathway. Results show that ISN neurons receive both excitatory and inhibitory afferent input mediated by glutamate and GABA respectively. The ISN neuron response to glycine probably derives from descending connections. Difference in the synaptic characteristics of ISN neurons controlling the parotid and von Ebner glands may relate to the different function of these two glands.     

Location of interneurones in the recurrent inhibitory circuit of the rabbit lateral geniculate nucleus

Summary Injection of horseradish peroxidase (HRP) into the dorsal lateral geniculate nucleus (LGN) of the rabbit gave rise to retrograde labeling of neurones in the caudal part of the thalamic reticular nucleus. Electrophysiological observations demonstrated that these neurones met all criteria for interneurones in the recurrent inhibitory circuit of the geniculo-cortical pathway. They responded to stimulation of the visual cortex (Cx) or the optic chiasm (OX) with a burst of repetitive discharges, in agreement with the long-lasting IPSP from Cx or OX in relay cells of LGN. Results of collision test showed that the reticular neurones received excitatory input via axonal collaterals of relay cells. The latency of their response to stimulation of Cx or OX is about 1.8 ms shorter than that of the corresponding IPSP in the relay cells. Stimulation of LGN evoked an antidromic spike in reticular neurones with a latency of bout 1.1 ms, indicating a monosynaptic projection from the latter to the relay cells. All evidence indicates that interneurones in the recurrent inhibitory circuit are most likely located in the caudal part of the thalamic reticular nucleus of the rabbit.     

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.     

Synaptic mechanisms regulating the activation of a Ca(2+)-mediated plateau potential in developing relay cells of the LGN

Using intracellular recordings in an isolated (in vitro) rat brain stem preparation, we examined the synaptic responses of developing relay neurons in the dorsal lateral geniculate nucleus (LGN). In newborn rats, strong stimulation of the optic tract (OT) evoked excitatory postsynaptic potentials (EPSPs) that gave rise to a sustained (300-1,300 ms), slow-decaying (<0.01 mV/s), depolarization (25-40 mV). Riding atop this response was a train of spikes of variable amplitude. We refer to this synaptically evoked event as a plateau potential. Pharmacology experiments indicate the plateau potential was mediated by the activation of high-threshold L-type Ca(2+) channels. Synaptic activation of the plateau potential relied on N-methyl-D-aspartate (NMDA) receptor-mediated activity and the spatial and/or temporal summation of retinally evoked EPSPs. Inhibitory postsynaptic responses (IPSPs) did not prevent the expression of the plateau potential. However, GABA(A) receptor activity modulated the intensity of optic tract stimulation needed to evoke the plateau potential, while GABA(B) receptor activity affected its duration. Expression of the plateau potential was developmentally regulated, showing a much higher incidence at P1-2 (90%) than at P19-20 (1%). This was in part due to the fact that developing relay cells show a greater degree of spatial summation than their mature counterparts, receiving input from as many as 7-12 retinal ganglion cells. Early spontaneous retinal activity is also likely to trigger the plateau potential. Repetitive stimulation of optic tract in a manner that approximated the high-frequency discharge of retinal ganglion cells led to a massive temporal summation of EPSPs and the activation of a sustained depolarization (>1 min) that was blocked by L-type Ca(2+) channel antagonists. These age-related changes in Ca(2+) signaling may contribute to the activity-dependent refinement of retinogeniculate connections.