Modeling aspects of learning by altering biophysical properties of a simulated neuron

A simulated neuron was constructed in which effects on spike discharge of altering certain fundamental biophysical parameters could be studied. The simulation was performed by use of a digital computer. The simulation was tested by comparing performance of the simulated neuron with that of actual neurons. Rates and patterns of spike discharge were achieved for the simulated neuron that were comparable to those recorded from units in the motor cortex of awake cats. Altering biophysical parameters such as firing threshold, levels of synaptic input or rates of transverse and longitudinal current spread produced appropriate alterations of discharge rate. On the above basis it was possible to investigate interrelated effects on spike discharge of changing levels of synaptic input and rates of current spread within the simulated neuron. With low rates of longitudinal current spread, graded levels of synaptic input produced correspondingly graded levels of ouput discharge. With high rates of longitudinal current spread, the transfer properties of the neuron were markedly altered. The neuron became a bistable operator where synaptic inputs above a certain level were enhanced and all those below were suppressed. A linear relationship was found to exist between firing threshold and the level of synaptic input required to reach the transition from quiescence to near-tetanic rates of discharge.Alterations in behavior are increasingly thought to be subserved by changes in the efficacy of synaptic transmission or in the post-synaptic intergrative propeties of neurons. The results of our investigations describe the interplay between those two processes.     

Electrical Properties of Hypothalamic Neuroendocrine Cells

Goldfish hypothalamic neuroendocrine cells have been investigated with intracellular recordings. The cells showed resting potentials of 50 mv and action potentials up to 117 mv followed by a long lasting and prominent diphasic hyperpolarizing afterpotential. The action potential occurred in two steps indicating sequential invasion. "Total" neuron (input) resistance was measured to be 3.3 x 10⁷ Ω and total neuron time constant was 42 msec. Orthodromic volleys, produced by olfactory tract stimulation, generated graded excitatory postsynaptic potentials. These neuroendocrine cells seem, therefore, to have electrical membrane properties that are similar to those of other central neurons. Antidromic volleys (pituitary stimulation) produced inhibitory post-synaptic potentials whose latency was only slightly longer than that of the antidromic spike indicating the presence of recurrent collaterals. This finding suggests that the concept of the neuroendocrine cell as a neuron whose axon forms contacts only on blood vessels and not on other neurons or effector cells is too restrictive. Perfusion of the gills with dilute (0.3 per cent) sea water produced an inhibition of spontaneous activity. This inhibition is discussed in relation to recent work which demonstrates that goldfish hypothalamic hormones facilitate Na⁺ influx across the gill membrane.     

剌激中缝背核压抑大鼠小脑浦肯野细胞对苔状...

In anaesthetized and paralyzed rats, the effect of dorsal raphe (DR) conditioning stimulation on cerebellar Purkinje cell (PC) responses to mossy fiber and climbing fiber inputs were examined. The main results are as follows: (1) Stimulation of cerebral sensorimotor cortex elicits widespread activation of mossy and climbing fiber inputs to PCs in contralateral VI and VII lobules of the cerebellum and generates two kinds of evoked responses, i.e. the simple spike (SS) and the complex spike (CS) responses with respectively a latency 8-25 and 12-30 ms. (2) These PC responses could be markedly suppressed by stimulation of DR at intensities which by themselves were subthreshold for directly affecting PC's spontaneous SS and CS activities. (3) This DR-induced depressive effects on evoked PC's SS and CS excitations could be attenuated or blocked by systemic administration of 5-HT receptor blocker methysergide. These results demonstrate that serotonergic fiber input from DR can suppress the efficacy of mossy and climbing fiber synaptic action on PC, or decrease the responsiveness of PC itself to afferent synaptic action. The findings of this study also suggest that the raphe-cerebellar serotonergic fiber afferent system may be involved in some of the important neuronal processing in the cerebellum.     

Electroreceptor mechanisms of the ampullae of lorenzini in skates

Responses of the receptor epithelium of single electrically isolated ampullae of Lorenzini and spike responses of nerve fibers connected to them to electrical stimulation under voltage clamping conditions were studied in experiments on the Black Sea skateRaja clavata. The preparations had an input resistance of 200–800 KΩ, a transepithelial resting potential of between 0 and ?2 mV, and the usual spontaneous spike activity in their afferent fibers. Thresholds of the electroreceptors were 2–10 µV (current about 10^?11 A). Within the working range of the electroreceptors (up to ±500 µV, current up to 1 nA) the current-voltage characteristic curve of the epithelium was linear without any evidence of spike or wave activity of the receptor cells. With negative currents of over 1–10 nA a regenerative spike appeared on the epithelium and was accompanied by an uncharacteristic pattern of spike discharge of the nerve fiber. It is concluded that, contrary to Bennett's hypothesis, spike or oscillatory activity bears no relationship to normal working of electroreceptors. It is postulated that "secondarily sensitive" receptor cells share a common functional organization, which is based on a chemical synapse with high electrical sensitivity.     

Radular mechanosensory neuron in the buccal ganglia of the terrestrial slug,Incilaria fruhstorferi

A radular mechanosensory neuron, RM, was identified in the buccal ganglia of Incilaria fruhstorferi. Fine neurites ramified bilaterally in the buccal ganglia, and main neurites entered the subradular epithelium via buccal nerve 3 (n3). When the radula was distorted by bending, RM produced an afferent spike which was preceded by an axonic spike recorded at n3. The response of RM to radular distortion was observed even in the absence of Ca²⁺, which drastically suppressed chemical synaptic interactions. Therefore, RM was concluded to be a primary radular mechanoreceptor.During rhythmic buccal motor activity induced by food or electrical stimulation of the cerebrobuccal connective, RM received excitatory input during the radular retraction phase. In the isolated buccal ganglia connected to the radula via n3s, the afferent spike, which had been evoked by electrical stimulation of the subradular epithelium, was broadened with the phasic excitatory input. Since the afferent spike was also broadened by current injection into the soma, depolarization due to the phasic input may have produced the spike broadening.Spike broadening was also observed during repetitive firing evoked by current injection. The amplitude of the excitatory postsynaptic potential in a follower neuron increased depending on the spike broadening of RM.Abbreviations CBC cerebrobuccal connective - EPSP excitatory postsynaptic potential - n1,n3 buccal nerves 1 and 3 - RBMA rhythmic buccal motor activity - RM radular mechanosensory neuron - SMT supramedian radular tensor neuron     

A model for the dynamic properties of integrating fibers: Target localization in a three-dimensional space—II. Computer simulation

• 1.1. The stimulation sequence provoked by a luminous point moving in front of a column of ommatidia was simulated for the eye of Squilla mantis.
• 2.2. The output from the ommatidia is transferred to one tangential, integrating fiber as graded potentials. These potentials follow a gaussian-shaped angular sensitivity function for each ommatidium.
• 3.3. The tangential fiber sums the inputs as they arrive and generates a spike if the sum is above threshold at one instant of time and at one point of the fiber.
• 4.4. The histograms of instantaneous frequencies of spike discharge resemble the input-pattern histograms.
• 5.5. The discharge pattern changes with distance and speed of the moving spot as well for the simulations as in electrophysiological recordings, and is adapted to the size of the animal.
• 6.6. The shape of the histograms (i.e. the pattern of spike discharge) is assumed to transmit the information on the position, speed and size of a moving target.

     

The Relationship between Respiration-Related Membrane Potential Slow Oscillations and Discharge Patterns in Mitral/Tufted Cells: What Are the Rules?

Background

A slow respiration-related rhythm strongly shapes the activity of the olfactory bulb. This rhythm appears as a slow oscillation that is detectable in the membrane potential, the respiration-related spike discharge of the mitral/tufted cells and the bulbar local field potential. Here, we investigated the rules that govern the manifestation of membrane potential slow oscillations (MPSOs) and respiration-related discharge activities under various afferent input conditions and cellular excitability states.

Methodology and Principal Findings

We recorded the intracellular membrane potential signals in the mitral/tufted cells of freely breathing anesthetized rats. We first demonstrated the existence of multiple types of MPSOs, which were influenced by odor stimulation and discharge activity patterns. Complementary studies using changes in the intracellular excitability state and a computational model of the mitral cell demonstrated that slow oscillations in the mitral/tufted cell membrane potential were also modulated by the intracellular excitability state, whereas the respiration-related spike activity primarily reflected the afferent input. Based on our data regarding MPSOs and spike patterns, we found that cells exhibiting an unsynchronized discharge pattern never exhibited an MPSO. In contrast, cells with a respiration-synchronized discharge pattern always exhibited an MPSO. In addition, we demonstrated that the association between spike patterns and MPSO types appeared complex.

Conclusion

We propose that both the intracellular excitability state and input strength underlie specific MPSOs, which, in turn, constrain the types of spike patterns exhibited.     

Integral evoked potentials and single unit activity in the frog olfactory bulb

Integral evoked potentials and intracellular potentials of single units were recorded from the frog olfactory bulb in response to afferent stimulation by two methods: electrical stimulation of the olfactory nerve and natural stimulation with odorous substances. At least four components can be distinguished in the response of the olfactory bulb to single electrical stimulation: an integral action potential of the olfactory nerve fibers, a synaptic glomerular potential, and two polysynaptic components. Responses of mitral and superficial (interglomerular) bulb cells to orthodromic electrical stimulation and antidromic stimulation of the olfactory tract are described. A functional similarity between the mitral cells of frogs and the analogous cells of rabbits is noted. Responses of the bulb to stimulation of olfactory receptors by odorous substances are characterized by regular waves of potentials. Corresponding waves of postsynaptic potentials are observed in the interglomerular cells of the bulb. These latter must, therefore, participate in generation of the rhythmic response. During stimulation by odorous substances, prolonged PSPs, producing excitation or inhibition of the spike discharge, arise in various cells of the bulb. The results of component analysis of the integral response and the functional properties of single bulb units are discussed.Institute of Problems of Information Transmission, Academy of Sciences of the USSR, Moscow; Institute of Biology of Internal Waters, Academy of Sciences of the USSR, Borok, Yaroslavl'Region. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 269–277, November–December, 1969.     

大鼠初级传入纤维与脊髓背角神经元间的动作电序列的突触传递

外周感觉神经元通过动作电位序列对信号进行编码,这些动作电位序列经过突触传递最终到达脑部。但是各种脉冲序列如何通过神经元之间的化学突触进行传递依然是一个悬而未决的问题。研究了初级传入A6纤维与背角神经元之间各种动作电位序列的突触传递过程。用于刺激的规则,周期、随机脉冲序列由短簇脉冲或单个脉冲构成。定义“事件”(event)为峰峰问期(intefspike interval)小于或等于规定阈值的最长动作电位串,然后从脉冲序列中提取事件间间期(interevent interval,IEI)。用时间,IEI图与回归映射的方法分析IEI序列,结果表明在突触后输出脉冲序列中可以检测到突触前脉冲序列的主要时间结构特征,特别是在短簇脉冲作为刺激单位时。通过计算输入与输出脉冲序列的互信息,发现短簇脉冲可以更可靠地跨突触传递由输入序列携带的神经信息。这些结果表明外周输入脉冲序列的主要时间结构特征可以跨突触传递,在突触传递神经信息的过程中短簇脉冲更为有效。这一研究在从突触传递角度探索神经信息编码方面迈出了一步。     

Emergence of network structure due to spike-timing-dependent plasticity in recurrent neuronal networks. I. Input selectivity–strengthening correlated input pathways

Spike-timing-dependent plasticity (STDP) determines the evolution of the synaptic weights according to their pre- and post-synaptic activity, which in turn changes the neuronal activity. In this paper, we extend previous studies of input selectivity induced by (STDP) for single neurons to the biologically interesting case of a neuronal network with fixed recurrent connections and plastic connections from external pools of input neurons. We use a theoretical framework based on the Poisson neuron model to analytically describe the network dynamics (firing rates and spike-time correlations) and thus the evolution of the synaptic weights. This framework incorporates the time course of the post-synaptic potentials and synaptic delays. Our analysis focuses on the asymptotic states of a network stimulated by two homogeneous pools of “steady” inputs, namely Poisson spike trains which have fixed firing rates and spike-time correlations. The (STDP) model extends rate-based learning in that it can implement, at the same time, both a stabilization of the individual neuron firing rates and a slower weight specialization depending on the input spike-time correlations. When one input pathway has stronger within-pool correlations, the resulting synaptic dynamics induced by (STDP) are shown to be similar to those arising in the case of a purely feed-forward network: the weights from the more correlated inputs are potentiated at the expense of the remaining input connections.     

The organization of exteroceptive information from the uropod to ascending interneurones of the crayfish

The organization of exteroceptive inputs to identified ascending interneurones of the crayfish, Procambarus clarkii (Girard), has been analyzed by stimulation of hairs on the uropod and simultaneous intracellular recordings from ascending interneurones. The spikes of single afferent neurones which innervated hairs on the distal ventral surface of the exopodite were consistently followed by a depolarizing synaptic potential in many identified ascending interneurones with a constant and short central delay of 0.7–1.5 ms. The amplitude of the potentials depended on the membrane potential of the ascending interneurones. Each afferent neurone made divergent outputs onto several ascending interneurones and each ascending interneurone received convergent inputs from several afferent neurones. Certain ascending interneurones made inhibitory or excitatory connections with other ascending interneurones. These central interactions were always one-way, and the spikes from one ascending interneurone consistently evoked excitatory or inhibitory post-synaptic potentials in other interneurones which followed with a constant and short latency of 0.7–1.0 ms. The inhibitory postsynaptic potential was reversed by injection of steady hyperpolarizing current.Abbreviations EPSP excitatory post-synaptic potential - IPSP inhibitory post-synaptic potential     

The development of the slow potentiation of the population spike of a long-term nonstimulating input in rats in a state of anesthetic sleep]

Changes in synaptic efficacy of the medial perforant pathway were studied after the long-term deprivation of the afferent inputs in hippocampus of rats under chloral hydrate or urethane anesthesia. Evoked field potential population spikes and population excitatory postsynaptic potentials were recorded in the dentate gyrus. The long-term deprivation obtained by cessation of stimulation of the tested input for up to 4 hours resulted in an enhancement (up to 190%, p < 0.01) of the population spike amplitude.     

Electrical potentials from the eye and optic nerve of Strombus: effects of electrical stimulation of the optic nerve.

1. Photic stimulation of the mature eye of Strombus can evoke in the optic nerve 'on' activity in numerous small afferent fibres and repetitive 'off' bursts of afferent impulses in a smaller number of larger fibres. 2. Synchronous invasion of the eye by electrically evoked impulses in small optic nerve fibres (apparently the 'on' afferents, antidromically activated) can evoke a burst of impulses in the larger 'off' fibres which propagate away from the eye. Invasion of the eye via one branch of optic nerve can evoke an answering burst in another branch. 3. Such electrically evoked bursts are similar to light-evoked 'off' bursts with respect to their impulse composition, their ability to be inhibited by illumination of the eye, and their susceptibility to MgCl2 anaesthesia. 4. Invasion of the eye by a train of repetitive electrically evoked impulses in the absence of photic stimulation can give rise to repetitive 'off' bursts as well as concomitant oscillatory potentials in the eye which are similar to those normally evoked by cessation of a photic stimulus. 5. The electrically evoked 'off' bursts appear to be caused by an excitatory rebound following the cessation of inhibitory synaptic input from photoreceptors which can be antidromically activated by electrical stimulation of the optic nerve. 6. The experimental results suggest that the rhythmic discharge of the 'off' fibres evoked by the cessation of a photic stimulus is mediated by the abrupt decrease of inhibitory synaptic input from the receptors.     

Caspase-3 activity in the rat hippocampal slices reflects changes in synaptic plasticity

Considering the involvement of caspase-3 in neuronal plasticity, we studied caspase-3 activity in the rat hippocampal slices, and electrophysiological characteristics of extracellular responses to paired-pulse stimulation of Schaffer's collaterals in the CA1 subfield of hippocampus. Caspase-3 activity was measured after electrophysiological recording in each slice separately. Maximal caspase-3 activity was observed in the slices with low responsiveness to single afferent stimulation indicative of decreased efficacy of interneuronal interaction. This phenomenon is unrelated to depression of neuronal excitability since paired-pulse stimulation increases the synaptic efficacy to second stimulus thus restoring population spike amplitudes to normal values. In "damaged" slices with impaired spike generation up to disappearing spikes to both stimuli, caspase-3 activity was close to the normal level of the "healthy" slices. The activity of another proteinase, cathepsin B, was increased in the "damaged" slices, no correlation with the modifications of electrophysiological indices being detected. Our data suggest that high caspase-3 activity in hippocampal slices is involved in maintenance of synaptic plasticity but not necessarily related to apoptosis.     

Reduction of Presynaptic Action Potentials by PAD: Model and Experimental Study

A compartmental model of myelinated nerve fiber was used to show that primary afferent depolarization (PAD), as elicited by axo-axonic synapses, reduces the amplitude of propagating action potentials primarily by interfering with ionic current responsible for the spike regeneration. This reduction adds to the effect of the synaptic shunt, increases with the PAD amplitude, and occurs at significant distances from the synaptic zone. PAD transiently enhances the sodium current activation, which partly accounts for the PAD-induced fiber hyperexcitability, and enhances sodium inactivation on a slower time course, thus reducing the amplitude of action potentials. In vivo, intra-axonal recordings from the intraspinal portion of group I afferent fibers were carried out to verify that depolarizations reduced the amplitude of propagating action potentials as predicted by the model. This article suggests PAD might play a major role in presynaptic inhibition.     

Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal X-irradiation.

Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilpateral forelimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 +/- 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells.     

Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal x-irradiation

Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilateral forlimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 ± 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells.     

Noradrenergic modulation of tactile responses in rat cortex. Current source-density and unit analyses

This study describes the noradrenergic modulation of tactile afferent information in the sensorimotor cortex of urethane-anesthetized rats. Synaptic and spike responses to a mechanical stimulation of the hand palm were evaluated by means of current source-density analysis and unit activity recording in all cortical layers. Results showed that activation of the locus coeruleus decreased and shortened afferent synaptic excitation in supragranular, but not in deep layers. On the average, unit responses exhibited facilitated latency, moderately increased amplitude, enhanced postexcitatory inhibition and synchronization of responses across layers. The apparent paradox of this global phasic facilitation correlated with a decrease in input synaptic currents was discussed according to hypotheses which might explain its functional significance.     

Co-cultures of inferior olive and cerebellum: electrophysiological evidence for multiple innervation of Purkinje cells by olivary axons.

Slices of inferior olive (IO) and cerebellum were co-cultured for several weeks by means of the roller tube technique. Recordings were carried out intracellularly from Purkinje cells (PCs) which were identified morphologically by intracellular injection of the fluorescent dye Lucifer yellow, or by immunohistochemical stainings with antibodies raised against the 28 kD Ca(2+)-binding protein calbindin. Following stimulation of olivary tissue, an all-or-none full complex spike response was recorded in some PCs consisting of a fast rising spike followed by a depolarizing potential. In other PCs, graded stimulation of the olivary explant induced synaptic potentials which were characterized by step-wise variation in their amplitude and resembled the ones occurring spontaneously. In contrast, only smoothly graded synaptic potentials were observed in cerebellar mono-cultures. These results indicate that some of the PCs in olivo-cerebellar co-cultures are innervated by several olivary neurons.