Quantal analysis and synaptic efficacy in the CNS.

Quantal analysis of synaptic transmission at connections between neurons in the CNS has provided insights concerning the structural constraints on transmitter release and postsynaptic responsiveness. However, it has proven difficult in many cases to resolve the size and variability of a single quantum or to distinguish clear peaks in amplitude histograms of evoked responses, due in part to the superposition of background instrumental and biological noise. These limitations raise questions about recent attempts to use direct or indirect methods of quantal analysis in order to distinguish between pre- and postsynaptic loci of the modifications underlying long-term potentiation, particularly since the interpretations are model-dependent and the statistical treatments and experimental techniques employed incorporate simplifying assumptions not yet proven.

A characterization of glycinergic receptors present in cultured rat medullary neurons.

1. Whole-cell current responses to bath application of glycine, beta-alanine, and taurine were studied in medullary neurons cultured from embryonic rats. 2.

Initial synaptic efficacy influences induction and expression of long-term changes in transmission.

Long-term depression (LTD) of glutamatergic and electrotonic transmission can be induced at mixed synapses between eighth nerve fibers and the goldfish Mauthner (M) cell in vivo, by pairing weak presynaptic tetani with postsynaptic inhibition. This LTD can be reversed by stronger tetani that produce long-term potentiation (LTP). Moreover, the depression is more likely to occur and tends to last longer when the initial synaptic efficacy is high--that is, if the synaptic strength is first potentiated.

Silent synaptic connections and their modifiability.

Comparison of the two afferent systems illustrates certain features common to synaptic transmission as well as differences that might be important for synaptic plasticity. Transmission at both the inhibitory and excitatory connections is satisfactorily described by a simple binomial model that considers the average probability of release to be the same at each active site, although it should be stressed that the best evidence derives from the first set of afferents. Another similarity between the two systems is that short-term changes in synaptic efficacy, namely, facilitation and depression, appear to be due to changes in p.

Role of medullary networks and postsynaptic membrane properties in regulating Mauthner cell responsiveness to sensory excitation.

A benefit of studying well-defined networks at a cellular level is that it might be possible both to place these details in the context of the specific function of the network and to extract general principles applicable to more complex systems. The Mauthner cell system in teleosts is one such vertebrate network where a single impulse can trigger a vital escape reaction, the C start, in response to auditory or visual stimuli. We review here experiments concerned with the organization, at the cellular level, of the afferent circuits impinging on the Mauthner cell and with certain intrinsic membrane properties of the Mauthner cell that contribute to shaping the threshold and expression of the C start.

Experimental endoretinal biopsy.

We performed transvitreal endoretinal biopsy in rabbit eyes to develop a reliable and safe technique to obtain retinal specimens from attached retina. Pars plana vitrectomy without lensectomy was followed by injection of Ringer's solution into the subretinal space to produce a focal retinal detachment. The apex of the focal detachment was excised by intraocular scissors and removed from the eye by pneumohydraulic expulsion.

Long-term potentiation of electrotonic coupling at mixed synapses.

Long-term potentiation of chemical synapses is closely related to memory and learning. Studies of this process have concentrated on chemically mediated excitatory synapses. By contrast, activity-dependent modification of gap junctions, which also widely exist in higher structures such as hippocampus and neocortex, has not been described.

The intensive care unit--who's in charge? The private practice view.

In the past 10 years, a number of authors have expressed concern that surgeons are abdicating their traditional role of providing preoperative and postoperative care in surgical intensive care units. To study today's private practice environment, we took a survey. Questionnaires were sent to the chiefs of surgery and the nurse managers of the surgical intensive care units at 188 non-university-affiliated hospitals throughout the United States.

Glutamate stimulates release of Ca2+ from internal stores in astroglia.

We report here that, in the absence of external Ca2+, glutamate produces a transient increase in intracellular Ca2+ [( Ca2+]i) in cultured spinal cord astrocytes, by mobilizing internal Ca2+ stores. [Ca2+]i was measured with Fura-2 using the ratiometric method. Astrocytes were identified by immunostaining for glial fibrillary acidic protein.

Developmental changes in the regulation of glycine-activated Cl- channels of cultured rat medullary neurons.

Glycine-activated currents in 1- to 11-day-old rat medullary neurons were studied using patch clamp techniques. Glycine produced neither repeatable whole-cell current responses nor single-channel activity in the cell-attached mode until cells were in culture for a week or more. However, Cl- channels were present at the early stages because glycine-activated channels were seen in excised, inside-out patches.

Transmission at a central inhibitory synapse. IV. Quantal structure of synaptic noise.

1. Continuous segments of synaptic noise were recorded, in 12 experiments, from the voltage-clamped goldfish Mauthner (M-)-cell soma during depolarizations beyond the Cl- equilibrium potential so that spontaneous inhibitory postsynaptic currents (IPSCs) were outward going, i.e.

Axotomy-induced alterations in the electrophysiological characteristics of neurons.

The electrophysiological alterations provoked by axotomy have now been studied for almost half a century, in a number of different cell types. Consequently, it is now possible to detail some common mechanisms underlying these changes and to sort out certain trends in the data. The major phenomena reviewed in this section and some possible future directions are summarized below.

The agar-albumin sandwich technique for processing retinal biopsy specimens.

Retinal biopsy may be useful procedure in the diagnosis of certain cases of infectious retinitis complicated by retinal detachment. The small, delicate pieces of retina obtained by retinal biopsy are difficult to handle and prepare for histologic processing. The tissue is friable, may curl upon itself, and is often lost during normal processing.

The effects of postsynaptic levels of cyclic AMP on excitatory and inhibitory responses of an identified central neuron.

The effects of cAMP on Mauthner (M-) cell excitatory and inhibitory responses were studied in vivo. Cyclic AMP was iontophoresed into the M-cell lateral dendrite, after which we monitored the changes in cellular responsiveness to stimulation of 2 classes of identified presynaptic cells: (1) excitatory fibers from the posterior branch of the ipsilateral eighth cranial nerve and (2) inhibitory interneurons activated by the M-cell collateral and commissural networks. We found that postsynaptic injections of cAMP increased the magnitudes of the electrically and chemically mediated EPSPs from the eighth nerve and enhanced M-cell inhibitory responses as well.

Characteristics of glycine-activated conductances in cultured medullary neurons from embryonic rat.

Characteristics of glycine-activated currents in 10- to 20-day-old neurons were studied using the gigaseal whole-cell technique. Glycine activated a Cl- conductance that was blocked by strychnine acting as a mixed inhibitor, effecting both Imax and Kd. Glycine receptors with at least two different sensitivities to strychnine were found, based on the apparent inhibition constants (Ki).

Unitary conductance changes at teleost Mauthner cell glycinergic synapses: a voltage-clamp and pharmacologic analysis.

1. The magnitude and kinetics of inhibitory postsynaptic currents (IPSCs) evoked in the goldfish Mauthner (M-) cell by intracellular stimulation of identified presynaptic interneurons (unitary responses) and by activation of the recurrent collateral network were determined with single-and double electrode voltage-clamp techniques. 2.

Synergism at central synapses due to lateral diffusion of transmitter.

Recordings of inhibitory postsynaptic currents in the goldfish (Carassius auratus) Mauthner cell demonstrate nonlinear interactions when adjacent synapses are coactivated. Responses evoked by single presynaptic neurons were paired with those due to activation of a limited pool of similar inhibitory cells. In about 50% of the experiments the compound currents were substantially larger than the sum of their individual components.

Identification of motoneurons and interneurons in the spinal network for escapes initiated by the mauthner cell in goldfish.

We used intracellular recording and staining techniques to study the spinal circuitry of the escape behavior (C-start) initiated by the Mauthner axon (M-axon) in goldfish. Simultaneous intracellular recordings from one or both M-axons and a spinal neuron, followed by HRP labeling of the spinal cell, show that each M-axon makes monosynaptic, chemical excitatory synapses onto 2 populations of ipsilateral spinal neurons. The first consists of the large primary motoneurons that, based on earlier work (Fetcho, 1986), innervate exclusively the faster, white muscle fiber types in the myomeres.

Synaptic transmission mediated by single club endings on the goldfish Mauthner cell. II. Plasticity of excitatory postsynaptic potentials.

Simultaneous pre- and postsynaptic intracellular recordings were used to analyze the properties of chemically mediated synaptic transmission between single club endings of eighth nerve afferents and the goldfish Mauthner (M-) cell lateral dendrite. The EPSPs exhibited pronounced facilitation when the presynaptic fiber fired high-frequency bursts of 2 or 3 impulses at intervals of 2-4 msec. The amplitudes of the EPSPs evoked by the second and third presynaptic impulses of a burst were, on average, 99 and 108% larger than that evoked by the first impulse.

Synaptic transmission mediated by single club endings on the goldfish Mauthner cell. I. Characteristics of electrotonic and chemical postsynaptic potentials.

Simultaneous pre- and postsynaptic intracellular recordings, combined with HRP injections, were used to study the properties of junctional transmission between club endings of saccular nerve afferents and the Mauthner (M-) cell in goldfish. All endings were electrotonically coupled to the M-cell, but impulses in less than 20% of the afferents produced chemically mediated excitatory postsynaptic potentials as well. There were no differences between the coupling potentials of those endings that mediated chemical transmission and those that did not, and presynaptic injections of HRP confirmed that in both cases the studied fibers terminated on the M-cell as single club endings.

An efferent inhibition of auditory afferents mediated by the goldfish Mauthner cell.

Intracellular recordings from goldfish auditory afferents revealed a hyperpolarization triggered by a single impulse in the Mauthner cell. The firing of either one of the two Mauthner cells alone was sufficient to evoke this potential change. The all or none hyperpolarization, which could only be recorded in some auditory fibers, presumably was an inhibitory postsynaptic potential.