Randomness of spontaneous activity and information transfer in neurons

The analysis of information coding in neurons requires methods that measure different properties of neuronal signals. In this paper we review the recently proposed measure of randomness and compare it to the coefficient of variation, which is the frequently employed measure of variability of spiking neuronal activity. We focus on the problem of the spontaneous activity of neurons, and we hypothesize that under defined conditions, spontaneous activity is more random than evoked activity. This hypothesis is supported by contrasting variability and randomness obtained from experimental recordings of olfactory receptor neurons in rats.     

Cost,competition and information in communication between relatives

Recent signalling models have shown that honest, cost-free communication between relatives can be stable. Moreover, cost-free signalling equilibria are in some cases more efficient than costly equilibria. However, we show that they are also relatively uninformative, particularly when relatedness between signaller and receiver is low. We explore the trade-off between signal cost and information, and further demonstrate that incorporating competition among signallers into a model of communication between relatives can reduce the propensity of any one signaller to display. As a result, there is a general increase in the amount of broadcast information in a non-costly signal with increasing competitor number.     

皮层抑制对大鼠丘脑底核自发放电的影响

目的:观察皮层抑制对正常及帕金森病(PD)大鼠丘脑底核(STN)神经元自发放电的影响。方法:采用玻璃微电极细胞外记录法,观察正常和PD大鼠STN神经元的放电活动及脑内微量注射KCl后,两组大鼠STN神经元放电频率的变化。结果:对照组和PD组大鼠STN神经元放电频率分别为(9.78±0.71)Hz和(23.81±1.08)Hz,PD组大鼠放电频率显著高于对照组(P<0.01),且呈爆发式放电的神经元比例明显高于对照组(P<0.05)。皮层注射KCl后,经过较长的潜伏期,两组大鼠STN神经元放电频率均明显降低,后缓慢恢复。结论:PD大鼠STN神经元放电频率增高,爆发式放电增多,而抑制皮层可使这种异常放电得到改善,提示皮层兴奋性的改变可能是PD中STN活动增强的另一个诱因。     

Synaptic communication between neurons and NG2+ cells

Chemical synaptic transmission provides the basis for much of the rapid signaling that occurs within neuronal networks. However, recent studies have provided compelling evidence that synapses are not used exclusively for communication between neurons. Physiological and anatomical studies indicate that a distinct class of glia known as NG2(+) cells also forms direct synaptic junctions with both glutamatergic and GABAergic neurons. Glutamatergic signaling can influence intracellular Ca(2+) levels in NG2(+) cells by activating Ca(2+) permeable AMPA receptors, and these inputs can be potentiated through high frequency stimulation. Although the significance of this highly differentiated form of communication remains to be established, these neuro-glia synapses might enable neurons to influence rapidly the behavior of this ubiquitous class of glial progenitors.     

The comparative roles of acetylcholine and noradrenaline in regulation of spontaneous spike activity of cortical neurons

The effects of acetylcholine and noradrenaline applications on neuronal sponta-neous activity were investigated in slices of guinea-pig parietal cortex. Iontophoretic ejections of both neurotransmitters to the cortical neurons evoked the same-type slowly-developing and long-lasting increase in the rate of spike activity. The different temperature sensitivity of cholinergic and noradrenergic reactions were revealed. During the temperature shift from 32-34 degrees C to 35-36 degrees C the cholinergic effect on neuronal spike activity became extremely strong, that is why even silent at t = 32-32 degrees C neurons became to acetylcholine responsive. Temperature-dependent changes in spike reaction to acetylcholine were accompanied by stable increase in spontaneous spike activity. The noradrenergic reactions did not change with temperature in limits from 32-34 to 35-36 degrees C. In this temperature range spike reactions to glutamate, the main excitation transmitter in the cortex, remained constant. The results obtained suggest that acetylcholine is the main neurotransmitter regulating spontaneous spike activity in cortical neurons.     

Cholesterol-mediated neurite outgrowth is differently regulated between cortical and hippocampal neurons

The acquisition of neuronal type-specific morphogenesis is a central feature of neuronal differentiation and has important consequences for region-specific nervous system functions. Here, we report that the cell type-specific cholesterol profile determines the differential modulation of axon and dendrite outgrowths in hippocampal and cerebral cortical neurons in culture. The extent of axon and dendrite outgrowths is greater and the polarity formation occurs earlier in cortical neurons than in hippocampal neurons. The cholesterol concentrations in total homogenate and the lipid rafts from hippocampal neurons are significantly higher than those from cortical neurons. Cholesterol depletion by beta-cyclodextrin markedly enhanced the neurite outgrowth and accelerated the establishment of neuronal polarity in hippocampal neurons, which were similarly observed in nontreated cortical neurons, whereas cholesterol loading had no effects. In contrast, both depletion and loading of cholesterol decreased the neurite outgrowths in cortical neurons. The stimulation of neurite outgrowth and polarity formation induced by cholesterol depletion was accompanied by an enhanced localization of Fyn, a Src kinase, in the lipid rafts of hippocampal neurons. A concomitant treatment with beta-cyclodextrin and a Src family kinase inhibitor, PP2, specifically blocked axon outgrowth but not dendrite outgrowth (both of which were enhanced by beta-cyclodextrin) in hippocampal neurons, suggesting that axon outgrowth modulated by cholesterol is induced in a Fyn-dependent manner. These results suggest that cellular cholesterol modulates axon and dendrite outgrowths and neuronal polarization under culture conditions and also that the difference in cholesterol profile between hippocampal and cortical neurons underlies the difference in neurite outgrowth between these two types of neurons.     

Excitotoxicity-related endocytosis in cortical neurons

Recent studies showed that endocytosis is enhanced in neurons exposed to an excitototoxic stimulus. We here confirm and analyze this new phenomenon using dissociated cortical neuronal cultures. NMDA-induced uptake (FITC-dextran or FITC or horseradish peroxidase) occurs in these cultures and is due to endocytosis, not to cell entry through damaged membranes; it requires an excitotoxic dose of NMDA and is dependent on extracellular calcium, but occurs early, while the neuron is still intact and viable. It involves two components, NMDA-induced and constitutive, with different characteristics. Neither component involves specific binding of the endocytosed molecules to a saturable receptor. Strikingly, molecules internalized by the NMDA-induced component are targeted to neuronal nuclei. This component, but not the constitutive one, is blocked by a c-Jun N-terminal protein kinase inhibitor. In conclusion, an excitotoxic dose of NMDA triggers c-Jun N-terminal protein kinase-dependent endocytosis in cortical neuronal cultures, providing an in vitro model of the excitotoxicity-induced endocytosis reported in intact tissues.     

Dynamics underlying synaptic gain between pairs of cortical pyramidal neurons

Changes in connectivity between pairs of neurons can serve as a substrate for information storage and for experience-dependent changes in neuronal circuitry. Early in development, synaptic contacts form and break, but how these dynamics influence the connectivity between pairs of neurons is not known. Here we used time-lapse imaging to examine the synaptic interactions between pairs of cultured cortical pyramidal neurons, and found that the axon-dendrite contacts between each neuronal pair were composed of both a relatively stable and a more labile population. Under basal conditions, loss and gain of contacts within this labile population was well balanced and there was little net change in connectivity. Selectively increasing the levels of activated CaMKII in the postsynaptic neuron increased connectivity between pairs of neurons by increasing the rate of gain of new contacts without affecting the probability of contact loss, or the proportion of stable and labile contacts, and this increase required Calcium/calmodulin binding to CaMKII. Our data suggest that activating CaMKII can increase synaptic connectivity through a CaM-dependent increase in contact formation, followed by stabilization of a constant fraction of new contacts.     

Various tolerances to arsenic trioxide between human cortical neurons and leukemic cells

Arsenic trioxide (As2O3) is very effective for treatment of acute promyelocytic leukaemia (APL) but little can pass through the blood-brain-barrier (BBB),which limits its use in the prevention and treatment of central nervous system leukaemia (CNSL). Before creating a non-invasive method to help As2O3 ’s access,the safe and effective therapeutic concentration of As2O3 in the CNS ought to be known. The changes of apoptosis biomarkers,[Ca2 ]i and PKC activity of both leukaemia cells and human cortical neurons,were monitored before and after being treated with As2O3 in vitro with laser confocal microscopy and Western blot. NSE concentration,the neuron invasive biomarker,was monitored by enzyme immunoassay (NSE-EIA). This study revealed that cortical neuron was more tolerable to As2O3 compared to NB4. 1.0 μmol / L As2O3 showed little influence on cortical neuron but effectively promoted apoptosis and induced differentiation of NB4.     

Various tolerances to arsenic trioxide between human cortical neurons and leukemic cells

Arsenic trioxide (As₂O₃) is very effective for treatment of acute promyelocytic leukaemia (APL) but little can pass through the blood-brain-barrier (BBB), which limits its use in the prevention and treatment of central nervous system leukaemia (CNSL). Before creating a non-invasive method to help As₂O₃’s access, the safe and effective therapeutic concentration of As₂O₃ in the CNS ought to be known. The changes of apoptosis biomarkers, [Ca²⁺]_i and PKC activity of both leukaemia cells and human cortical neurons, were monitored before and after being treated with As₂O₃ in vitro with laser confocal microscopy and Western blot. NSE concentration, the neuron invasive biomarker, was monitored by enzyme immunoassay (NSE-EIA). This study revealed that cortical neuron was more tolerable to As₂O₃ compared to NB4. 1.0 μmol / L As₂O₃ showed little influence on cortical neuron but effectively promoted apoptosis and induced differentiation of NB4.     

Inhibition synchronizes sparsely connected cortical neurons within and between columns in realistic network models

Networks of compartmental model neurons were used to investigate the biophysical basis of the synchronization observed between sparsely-connected neurons in neocortex. A model of a single column in layer 5 consisted of 100 model neurons: 80 pyramidal and 20 inhibitory. The pyramidal cells had conductances that caused intrinsic repetitive bursting at different frequencies when driven with the same input. When connected randomly with a connection density of 10%, a single model column displayed synchronous oscillatory action potentials in response to stationary, uncorrelated Poisson spike-train inputs. Synchrony required a high ratio of inhibitory to excitatory synaptic strength; the optimal ratio was 41, within the range observed in cortex. The synchrony was insensitive to variation in amplitudes of postsynaptic potentials and synaptic delay times, even when the mean synaptic delay times were varied over the range 1 to 7 ms. Synchrony was found to be sensitive to the strength of reciprocal inhibition between the inhibitory neurons in one column: Too weak or too strong reciprocal inhibition degraded intra-columnar synchrony. The only parameter that affected the oscillation frequency of the network was the strength of the external driving input which could shift the frequency between 35 to 60 Hz. The same results were obtained using a model column of 1000 neurons with a connection density of 5%, except that the oscillation became more regular.Synchronization between cortical columns was studied in a model consisting of two columns with 100 model neurons each. When connections were made with a density of 3% between the pyramidal cells of each column there was no inter-columnar synchrony and in some cases the columns oscillated 180° out of phase with each other. Only when connections from the pyramidal cells in each column to the inhibitory cells in the other column were added was synchrony between the columns observed. This synchrony was established within one or two cycles of the oscillation and there was on average less than 1 ms phase difference between the two columns. Unlike the intra-columnar synchronization, the inter-columnar synchronization was found to be sensitive to the synaptic delay: A mean delay of greater than 5 ms virtually abolished synchronization between columns.     

Reduction of information redundancy in the ascending auditory pathway

Information processing by a sensory system is reflected in the changes in stimulus representation along its successive processing stages. We measured information content and stimulus-induced redundancy in the neural responses to a set of natural sounds in three successive stations of the auditory pathway-inferior colliculus (IC), auditory thalamus (MGB), and primary auditory cortex (A1). Information about stimulus identity was somewhat reduced in single A1 and MGB neurons relative to single IC neurons, when information is measured using spike counts, latency, or temporal spiking patterns. However, most of this difference was due to differences in firing rates. On the other hand, IC neurons were substantially more redundant than A1 and MGB neurons. IC redundancy was largely related to frequency selectivity. Redundancy reduction may be a generic organization principle of neural systems, allowing for easier readout of the identity of complex stimuli in A1 relative to IC.     

Extra DNA in forebrain cortical neurons

Combined cytochemical and biochemical techniques show that neurons from the forebrain cortex of various mammals (rat, mouse, and rabbit) contain near, but not full, 4c DNA levels (c, DNA content of haploid chromosome set). This extra DNA is predominantly synthesized post-natally. More specifically, in rats a wave of DNA synthesis starts a few hours before birth and extends well into the post-natal period, levelling off after 30 days. Density labelling experiments using [5-³H]-bromo-2′-deoxyuridine (BUdR) suggest that the DNA synthesis proceeds semiconservatively, with the prenatally formed DNA serving as a template for post-natal strand replication. Although all three mammalian DNA polymerases (α, β, and γ) can be detected in the cortical neurons of young rats their developmental course does not allow one to unambiguously identify the enzyme(s) responsible for the observed DNA increase. Density gradient centrifugations of neuronal DNA post-natally labelled with [³H]thymidine give no indication of a preferential enrichment of defined segments of the genome. In spite of this, the present data do not rule out the possibility that functionally important sequences might be selectively replicated.     

Cooperative nonlinearities in auditory cortical neurons

Cortical receptive fields represent the signal preferences of sensory neurons. Receptive fields are thought to provide a representation of sensory experience from which the cerebral cortex may make interpretations. While it is essential to determine a neuron's receptive field, it remains unclear which features of the acoustic environment are specifically represented by neurons in the primary auditory cortex (AI). We characterized cat AI spectrotemporal receptive fields (STRFs) by finding both the spike-triggered average (STA) and stimulus dimensions that maximized the mutual information between response and stimulus. We derived a nonlinearity relating spiking to stimulus projection onto two maximally informative dimensions (MIDs). The STA was highly correlated with the first MID. Generally, the nonlinearity for the first MID was asymmetric and often monotonic in shape, while the second MID nonlinearity was symmetric and nonmonotonic. The joint nonlinearity for both MIDs revealed that most first and second MIDs were synergistic and thus should be considered conjointly. The difference between the nonlinearities suggests different possible roles for the MIDs in auditory processing.     

皮层神经元动作电位不应期和阈电位与神经元动作电位编码的关系

目的：测量和比较感觉运动皮层Ⅱ/Ⅲ层锥体神经元和中间神经元的内在特性并研究其与动作电位编码频率和精确性的关系。方法：采用全细胞电流钳记录模式,获得的数据输入pClamp和Origin进行处理分析。结果：与锥体神经元相比,中间神经元群集动作电位具有较低的阈电位水平和较短的不应期,从而中间神经元具有较高的动作电位编码频率和精确性。结论：皮层神经元动作电位的阈电位水平和不应期调控动作电位的编码频率和精确性。     

Predicting the synaptic information efficacy in cortical layer 5 pyramidal neurons using a minimal integrate-and-fire model

Synaptic information efficacy (SIE) is a statistical measure to quantify the efficacy of a synapse. It measures how much information is gained, on the average, about the output spike train of a postsynaptic neuron if the input spike train is known. It is a particularly appropriate measure for assessing the input–output relationship of neurons receiving dynamic stimuli. Here, we compare the SIE of simulated synaptic inputs measured experimentally in layer 5 cortical pyramidal neurons in vitro with the SIE computed from a minimal model constructed to fit the recorded data. We show that even with a simple model that is far from perfect in predicting the precise timing of the output spikes of the real neuron, the SIE can still be accurately predicted. This arises from the ability of the model to predict output spikes influenced by the input more accurately than those driven by the background current. This indicates that in this context, some spikes may be more important than others. Lastly we demonstrate another aspect where using mutual information could be beneficial in evaluating the quality of a model, by measuring the mutual information between the model’s output and the neuron’s output. The SIE, thus, could be a useful tool for assessing the quality of models of single neurons in preserving input–output relationship, a property that becomes crucial when we start connecting these reduced models to construct complex realistic neuronal networks.