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Probabilistic secretion of quanta: spontaneous release at active zones of varicosities, boutons, and endplates.

The amplitude-frequency histogram of spontaneous miniature endplate potentials follows a Gaussian distribution at mature endplates. This distribution gives the mean and variance of the quantum of transmitter. According to the vesicle hypothesis, this quantum is due to exocytosis of the contents of a single synaptic vesicle. Multimodal amplitude-frequency histograms are observed in varying degrees at developing endplates and at peripheral and central synapses, each of which has a specific active zone structure. These multimodal histograms may be due to the near synchronous exocytosis of more than one vesicle. In the present work, a theoretical treatment is given of the rise of intraterminal calcium after the stochastic opening of a calcium channel within a particular active zone geometry. The stochastic interaction of this calcium with the vesicle-associated proteins involved in exocytosis is then used to calculate the probability of quantal secretions from one or several vesicles at each active zone type. It is shown that this procedure can account for multiquantal spontaneous release that may occur at varicosities and boutons, compared with that at the active zones of motor nerve terminals.

Animals↗

Effects of variance in mini amplitude on stimulus-evoked release: a comparison of two models.

The strength of synaptic connections between two neurons is characterized by the number of release sites (N) on the presynaptic cell, the probability (p) of transmitter release at those sites in response to a stimulus, and the average size (A) of the postsynaptic response from each site. Quantal analysis can determine N, p, and A, but the large variance in the amplitudes of minis at central synapses is predicted to obscure quantal peaks and render quantal analysis unusable. Recently it has been suggested that the variance in mini amplitude is generated by differences between release sites, rather than by quantum-to-quantum fluctuations at identical sites, and that this form of variance in mini amplitude reduces the amount of variance expected in quantal peaks. Using simulations, we examine the possibility of resolving quantal peaks assuming either form of variance in mini amplitude. We find that individual quantal peaks are resolvable in neither case, provided that the uniquantal distribution is similar to the mini distribution. Because this lack of resolution compromises the utility of quantal analysis, we develop a general description that can solve N and p, given the statistical parameters of the mini distribution and the evoked distribution. We find that this description is relatively insensitive to the source of variance in mini amplitude.

Analysis of Variance↗

Calcium dynamics associated with a single action potential in a CNS presynaptic terminal.

Calcium dynamics associated with a single action potential were studied quantitatively in the calyx of Held, a large presynaptic terminal in the rat brainstem. Terminals were loaded with different concentrations of high- or low-affinity Ca2+ indicators via patch pipettes. Spatially averaged Ca2+ signals were measured fluorometrically and analyzed on the basis of a single compartment model. A single action potential led to a total Ca2+ influx of 0.8-1 pC. The accessible volume of the terminal was about 0.4 pl; thus the total calcium concentration increased by 10-13 microM. The Ca(2+)-binding ratio of the endogenous buffer was about 40, as estimated from the competition with Fura-2, indicating that 2.5% of the total calcium remained free. This is consistent with the peak increase in free calcium concentration of about 400 nM, which was measured directly with MagFura-2. The decay of the [Ca2+]i transients was fast, with time constants of 100 ms at 23 degrees C and 45 ms at 35 degrees C, indicating Ca2+ extrusion rates of 400 and 900 s-1, respectively. The combination of the relatively low endogenous Ca(2+)-binding ratio and the high rate of Ca2+ extrusion provides an efficient mechanism for rapidly removing the large Ca2+ load of the terminal evoked by an action potential.

Action Potentials↗

Long-term potentiation and depression induced by a stochastic conditioning of a model synapse.

Protracted presynaptic activity can induce long-term potentiation (LTP) or long-term depression (LTD) of the synaptic strength. However, virtually all the experiments testing how LTP and LTD depend on the conditioning input are carried out with trains of stimuli at constant frequencies, whereas neurons in vivo most likely experience a stochastic variation of interstimulus intervals. We used a computational model of synaptic transmission to test if and to what extent the stochastic fluctuations of an input signal could alter the probability to change the state of a synapse. We found that, even if the mean stimulation frequency was maintained constant, the probability to induce LTD and LTP could be a function of the temporal variation of the input activity. This mechanism, which depends only on the statistical properties of the input and not on the onset of additional biochemical mechanisms, is not usually considered in the experiments, but it could have an important role to determine the amount of LTP/LTD induction in vivo. In response to a change in the distribution of the interstimulus intervals, as measured by the coefficient of variation, a synapse could be easily adapted to inputs that might require immediate attention, with a shift of the input thresholds required to elicit LTD or LTP, which are restored to their initial conditions as soon as the input pattern returns to the original temporal distribution.

Long-Term Potentiation↗

An analysis of the effect of retinal ganglion cell impulses upon the firing probability of neurons in the dorsal lateral geniculate nucleus of the cat.

This study examines the probabilistic way in which LGN cells produce impulses. Simultaneous extracellular recordings were made from a single lateral geniculate nucleus (LGN) relay cell and the one retinal cell that triggered most of its impulses during vigorous responses. Impulses in the retinal train were classified as 'successful' in triggering an LGN impulse, or 'unsuccessful'. Similarly, the impulses in the LGN train were either 'Triggered' by a successful retinal impulse, or were 'Anonymous'. These impulses delimited various intervals whose distributions were compared to the relevant distribution of all intervals to determine whether short or long intervals tended to dominate in each case. Intervals between unsuccessful and successful impulses tended to be shorter than other retinal intervals, with their probability declining exponentially with duration. These data imply a decaying excitation produced by each impulse, but with a short refractory period following each Triggered impulse. Short intervals between Anonymous impulses were relatively common; Anonymous impulses thus lack the same refractoriness and tend to occur in bursts. The exponential excitation following an unsuccessful retinal impulse also facilitates Anonymous impulses, while Anonymous impulses (during visual stimulation) render the LGN slightly refractory for subsequent retinal impulses.

Action Potentials↗

Gonadal steroids regulate behavioral responses to pheromones by actions on a subdivision of the medial preoptic nucleus.

Mating behavior in male hamsters is initiated by pheromones, detected by two chemosensory systems which converge on the medial nucleus of the amygdala and the bed nucleus of the stria terminalis. Neurons in these areas project to the medial preoptic nucleus. All three of these areas contain androgen receptors. Using Fos as a marker of stimulation we have found that pheromones stimulate neurons in all three areas in intact males but fail to stimulate the magnocellular division of the medial preoptic nucleus of castrates. As this area plays a critical role in the regulation of male mating behavior our results suggest that steroids regulate mating by maintaining the responsiveness of the magnocellular division of the medial preoptic nucleus to pheromones.

Animals↗

A revised method for analysing neglect using the landmark task.

In order to better disentangle 'perceptual' and 'response' biases in neglect patients, Bisiach and his co-workers developed a new version of the 'landmark task'. In their version, subjects are required to choose which is the longer (first condition) or the shorter (second condition) of the two portions of a pre-bisected horizontal line. Two indices were proposed, for the purpose of measuring perceptual and response bias respectively. The perceptual bias index (PB) is the constant error across conditions, while the response bias index (RB) is the degree of response consistency between conditions. Although valuable in a clinical context, these indices are not mathematically independent of one another. Furthermore, they do not exploit all of the information available in a given set of landmark data, since the responses made at the different landmark locations are all averaged together. To overcome these problems, we propose two new indices that can be derived from the revised landmark task. Our perceptual bias index is the Point of Subjective Equality (PSE)--the mean landmark location that appears to be halfway along the line. The response bias index, M, is the mean probability of making a response that opposes the patient's subjective midpoint. PSE and M are mathematically independent of each other and use most of the landmark information. The method and its theoretical foundation are summarized, and illustrative data obtained from brain damaged patients and control subjects are presented. Finally, computational procedures are provided for both PSE and M.

Brain↗

From unilateral neglect to the brain basis of consciousness.

According to the dominant focus model, the differential activation of the thalamocortical network is a sufficient condition for the diversity of states of consciousness to occur, and coherent patterns of interactive forebrain activation peaks are sufficient to generate specific conscious figures against ground. These minimal assumptions are consonant with the known properties of unilateral neglect. It becomes unnecessary to suppose that consciousness is an independent entity, occupies a dedicated location in the brain, is contingent on a minimal level of neural complexity, plays a causal role in enabling perception or action, or evolved because it plays any such role.

Attention↗

A reconceptualisation of apraxia of speech: a synthesis of evidence.

This paper presents a reconceptualisation of apraxia of speech (AOS) and reviews a range of acoustic and articulatory data which have been reported on apraxia of speech. Data from both domains, and previous theoretical debate are discussed as support for this cognitive-based reconceptualisation.

Apraxias↗

Hebb, pandemonium and catastrophic hypermnesia: the hippocampus as a suppressor of inappropriate associations.

The hippocampus has been proposed as a key component of a "behavioural inhibition system". We explore the implications of this idea for the nature of associative memory--i.e. learning that is distinct from the moulding of response sequences by error correction and reinforcement. It leads to the view that all associative memory depends on purely Hebbian mechanisms. Memories involve acquisition of new goals not the strengthening of new stimulus-response links. Critically, memories will consist of affectively positive and affectively negative associations as well "purely cognitive" information. The hippocampus is seen as a supervisor that is normally "just checking" information about current available goals. When one available goal is pre-eminent there is no hippocampal output and the goal controls the response system. When two or more goals are similarly and highly primed there is conflict. This is detected by the hippocampus which sends output that increases the valence of affectively negative perceptions and so resolves the conflict by suppressing more aversive goals. Such conflict resolution occurs with innate as well as acquired goals and is fundamentally non-memorial. But, in memory paradigms, it can often act to suppress interference on the current trial and, through Hebbian association of the increase in negative affect, decrease the probability of interference on later trials and during consolidation. Both memory-driven and innate behaviour is made hippocampal-dependent by innate and acquired conflicting tendencies and not the class of stimulus presented.

Amnesia↗

Stimulus effects in unilateral neglect?

Unilaterally brain-damaged subjects and normal controls were administered parallel verbal and nonverbal forms of a visual cancellation task. The attentional theory of unilateral neglect, which predicts less manifest neglect on tasks that preferentially engage the damaged hemisphere, was not supported. Subjects who exhibited neglect did so to a comparable degree on both verbal and nonverbal tasks. The data are consistent with a model of right hemisphere dominance for attention across the visual field.

Aged↗

Orthographic ambiguity: comments on Baxter and Warrington.

In this note, I comment on a recent study by Baxter and Warrington of an acquired dysgraphic patient, KT, that appeared in Cortex, 23, 1987. The focus of my discussion centers around Baxter and Warrington's findings that: (1) KT shows a striking orthographic "regularity" effect in his spelling performance and; (2) KT's use of sound-to-spelling mapping options does not reflect the distribution of use of these options in the word corpus examined. If well-founded, the implications of these results call into question specific features of the dominant model of spelling. However, a close scrutiny of the procedures used by Baxter and Warrington in analyzing their data indicates that they collapsed across factors that have elsewhere been shown to influence spelling performance (i.e., within-syllable frequency of occurrence of phoneme-grapheme mapping options). Therefore, results obtained for patient KT cannot, in their current form, be used to speak to the specific issues of spelling that Baxter and Warrington originally set out to address.

Brain↗

Panic disorder: a theoretical synthesis of medical and psychological approaches.

Panic disorder is a common and disabling condition which frequently leads to excessive reliance upon medical facilities. It is also closely associated with the development of agoraphobia. Medical approaches implicate disturbances of ascending brain noradrenergic and serotonergic systems, and support related pharmacotherapies. Contemporary psychological approaches focus upon misinterpretations of bodily sensations and an undue appreciation of the risk of life-threatening illness, and support cognitive/behavioral psychotherapies. A synthesis is possible by developing the view that the implicated ascending aminergic systems normally play a part in "effortful" or context-sensitive behavior. A relative failure of this under conditions of heightened arousal might be responsible for the rigid patterns of fear, belief, and behavior that characterize these patients. Clinical and research implications are discussed.

Agoraphobia↗