Prefrontal coding of temporally discounted values during intertemporal choice

Reward from a particular action is seldom immediate, and the influence of such delayed outcome on choice decreases with delay. It has been postulated that when faced with immediate and delayed rewards, decision makers choose the option with maximum temporally discounted value. We examined the preference of monkeys for delayed reward in an intertemporal choice task and the neural basis for real-time computation of temporally discounted values in the dorsolateral prefrontal cortex. During this task, the locations of the targets associated with small or large rewards and their corresponding delays were randomly varied. We found that prefrontal neurons often encoded the temporally discounted value of reward expected from a particular option. Furthermore, activity tended to increase with [corrected] discounted values for targets [corrected] presented in the neuron's preferred direction, suggesting that activity related to temporally discounted values in the prefrontal cortex might determine the animal's behavior during intertemporal choice.     

Context-dependent coding in single neurons

The linear-nonlinear cascade model (LN model) has proven very useful in representing a neural system’s encoding properties, but has proven less successful in reproducing the firing patterns of individual neurons whose behavior is strongly dependent on prior firing history. While the cell’s behavior can still usefully be considered as feature detection acting on a fluctuating input, some of the coding capacity of the cell is taken up by the increased firing rate due to a constant “driving” direct current (DC) stimulus. Furthermore, both the DC input and the post-spike refractory period generate regular firing, reducing the spike-timing entropy available for encoding time-varying fluctuations. In this paper, we address these issues, focusing on the example of motoneurons in which an afterhyperpolarization (AHP) current plays a dominant role regularizing firing behavior. We explore the accuracy and generalizability of several alternative models for single neurons under changes in DC and variance of the stimulus input. We use a motoneuron simulation to compare coding models in neurons with and without the AHP current. Finally, we quantify the tradeoff between instantaneously encoding information about fluctuations and about the DC.     

Prefrontal neurons predict choices during an auditory same-different task

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a "reference" stimulus that were followed by a "test" stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task.     

Information coding by ensembles of resonant neurons

In the present paper, we propose a novel neural procedure for signal processing and coding based on the subthreshold oscillations and resonance of the neural membrane potential that could be used by real neurons to perform frequency spectra analysis and information coding of incoming signals. Taking into account the biophysical properties of the neural membranes, we note that the subthreshold resonant behaviour they exhibit can be used to analyse incoming signals and represent them in the frequency domain. We study the reliability of the representation of signals depending on the biophysical parameters of the neurons, the fault-tolerance of this coding scheme and its robustness against noise and in the presence of spikes. The principal characteristics of our system are the use of the physical phenomenon of neural resonance (rarely considered in the literature for signal coding); it fits well with the biophysical parameters of most neurons that exhibit subthreshold oscillations; it is compatible with experimental data; and it can be easily integrated in a more general model of information processing and coding that includes communication between neurons based on spikes.     

Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring

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In vivo suppression of coding associated with bacteriophage-induced S-adenosylmethionine hydrolase

The methylation of ribosomal and transfer ribonucleic acid (RNA) synthesized after the induction of a hydrolase for S-adenosylmethionine by phage T3 infection is reducible to 50% of the methylation of RNA in uninfected cells. Hypomethylated ribosomal RNA is found in 70S particles that dissociate in 100 mum Mg(++) to yield only 30S and 50S subunits. By this criterion, the omitted methyl groups apparently are not required for ribosomal maturation or stability. The rate of production of alkaline phosphatase in a phosphatase amber mutant was examined after phage infection in the presence and in the absence of streptomycin to determine the effect on the translation process consequent to S-adenosyl-l-methionine (SAM) hydrolase induction. Significant increases in the rates of phosphatase production were found when ultraviolet-inactivated T3 or streptomycin was added. The effects were cumulative when the cells were treated with both bacteriophage and the drug. Ultraviolet-inactivated T7, a phage closely related to T3 but which does not produce the SAM hydrolase, did not enhance the rate of alkaline phosphatase production. We suggest that the production of SAM hydrolase affects the stability of the translation process by the observed hypomethylation or by mechanisms concerning polyamine metabolism.     

Possible mechanism of bursting suppression in nociceptive neurons

The use of the mathematical model of rat nociceptive neuron membrane allowed us to predict a new mechanism of suppression of ectopic bursting discharges, which arise in neurons of dorsal root ganglia and are one of the causes of neuropathic pain. The treatment with comenic acid leads to switching off the ectopic bursting discharges due to a decrease in the effective charge transferring via the activation gating structure of the slow sodium channels (Na _V1.8a). Comenic acid is a drug substance of a new non-opioid analgesic [1] Thus, this analgesic not only reduces the frequency of rhythmic discharges of nociceptive neuron membrane [2] but also it suppresses its ectopic bursting discharges.     

Energy coding in neural network with inhibitory neurons

This paper aimed at assessing and comparing the effects of the inhibitory neurons in the neural network on the neural energy distribution, and the network activities in the absence of the inhibitory neurons to understand the nature of neural energy distribution and neural energy coding. Stimulus, synchronous oscillation has significant difference between neural networks with and without inhibitory neurons, and this difference can be quantitatively evaluated by the characteristic energy distribution. In addition, the synchronous oscillation difference of the neural activity can be quantitatively described by change of the energy distribution if the network parameters are gradually adjusted. Compared with traditional method of correlation coefficient analysis, the quantitative indicators based on nervous energy distribution characteristics are more effective in reflecting the dynamic features of the neural network activities. Meanwhile, this neural coding method from a global perspective of neural activity effectively avoids the current defects of neural encoding and decoding theory and enormous difficulties encountered. Our studies have shown that neural energy coding is a new coding theory with high efficiency and great potential.     

Auditory information coding by modeled cochlear nucleus neurons

In this paper we use information theory to quantify the information in the output spike trains of modeled cochlear nucleus globular bushy cells (GBCs). GBCs are part of the sound localization pathway. They are known for their precise temporal processing, and they code amplitude modulations with high fidelity. Here we investigated the information transmission for a natural sound, a recorded vowel. We conclude that the maximum information transmission rate for a single neuron was close to 1,050 bits/s, which corresponds to a value of approximately 5.8 bits per spike. For quasi-periodic signals like voiced speech, the transmitted information saturated as word duration increased. In general, approximately 80% of the available information from the spike trains was transmitted within about 20 ms. Transmitted information for speech signals concentrated around formant frequency regions. The efficiency of neural coding was above 60% up to the highest temporal resolution we investigated (20 μs). The increase in transmitted information to that precision indicates that these neurons are able to code information with extremely high fidelity, which is required for sound localization. On the other hand, only 20% of the information was captured when the temporal resolution was reduced to 4 ms. As the temporal resolution of most speech recognition systems is limited to less than 10 ms, this massive information loss might be one of the reasons which are responsible for the lack of noise robustness of these systems.     

Neurochemical coding of myenteric neurons in the guinea-pig antrum

Electrophysiological studies of myenteric neurons in the guinea-pig antrum suggest that different neuroactive compounds are involved in synaptic transmission. It is not known what neurotransmitters and neuropeptides are present and to what extent they colocalize. Immunohistochemical stainings were performed on whole-mount preparations of the guinea-pig antrum. Immunoreactivity for neuron-specific enolase was used as a general marker and was set at 100%. There was no overlap between cholinergic and nitrergic neurons, resulting in two separate subpopulations. The presence of choline acetyltransferase immunoreactivity was used to identify the cholinergic subset, which accounted for 56% of the cells. Immunoreactivity for nitric oxide synthase, on the other hand, was displayed in 40.7% of the neurons. Substance-P immunoreactivity was present in 37.4% of the cells and vasoactive intestinal peptide and neuropeptide Y in 21.7% and 28.6%, respectively. Small subsets of neurons had immunoreactivity for serotonin (3.9%), calretinin (6.8%) and calbindin (0.5%). Colocalization studies revealed several subgroups of neurons, containing one or more of the screened markers. Though some similarity is found in the chemical coding of the antrum compared to that of the small intestine and the corpus, remarkable differences can be seen in the occurrence of some subpopulations. Cholinergic neurons are not as predominant as in other parts of the gut, serotonin presence is doubled and some vasointestinal-peptide-positive neurons express substance P. These differences might reflect the highly specialized function of the antrum; however, the exact role of these classes remains to be established.     

Evolutionarily conserved coding properties of auditory neurons across grasshopper species

We investigated encoding properties of identified auditory interneurons in two not closely related grasshopper species (Acrididae). The neurons can be homologized on the basis of their similar morphologies and physiologies. As test stimuli, we used the species-specific stridulation signals of Chorthippus biguttulus, which evidently are not relevant for the other species, Locusta migratoria. We recorded spike trains produced in response to these signals from several neuron types at the first levels of the auditory pathway in both species. Using a spike train metric to quantify differences between neuronal responses, we found a high similarity in the responses of homologous neurons: interspecific differences between the responses of homologous neurons in the two species were not significantly larger than intraspecific differences (between several specimens of a neuron in one species). These results suggest that the elements of the thoracic auditory pathway have been strongly conserved during the evolutionary divergence of these species. According to the 'efficient coding' hypothesis, an adaptation of the thoracic auditory pathway to the specific needs of acoustic communication could be expected. We conclude that there must have been stabilizing selective forces at work that conserved coding characteristics and prevented such an adaptation.     

Direct measurement of specific membrane capacitance in neurons

The specific membrane capacitance (C(m)) of a neuron influences synaptic efficacy and determines the speed with which electrical signals propagate along dendrites and unmyelinated axons. The value of this important parameter remains controversial. In this study, C(m) was estimated for the somatic membrane of cortical pyramidal neurons, spinal cord neurons, and hippocampal neurons. A nucleated patch was pulled and a voltage-clamp step was applied. The exponential decay of the capacitative charging current was analyzed to give the total membrane capacitance, which was then divided by the observed surface area of the patch. C(m) was 0.9 microF/cm(2) for each class of neuron. To test the possibility that membrane proteins may alter C(m), embryonic kidney cells (HEK-293) were studied before and after transfection with a plasmid coding for glycine receptor/channels. The value of C(m) was indistinguishable in untransfected cells and in transfected cells expressing a high level of glycine channels, indicating that differences in transmembrane protein content do not significantly affect C(m). Thus, to a first approximation, C(m) may be treated as a "biological constant" across many classes of neuron.     

Post-transcriptional suppression of pathogenic prion protein expression in Drosophila neurons

A wealth of evidence supports the view that conformational change of the prion protein, PrPC, into a pathogenic isoform, PrPSc, is the hallmark of sporadic, infectious, and inherited forms of prion disease. Although the central role played by PrPSc in the pathogenesis of prion disease is appreciated, the cellular mechanisms that recognize PrPSc and modulate its production, clearance, and neural toxicity have not been elucidated. To address these questions, we used a tissue-specific expression system to express wild-type and disease-associated PrP molecules heterologously in Drosophila melanogaster. Our results indicate that Drosophila brain possesses a specific and saturable mechanism that suppresses the accumulation of PG14, a disease-associated insertional PrP mutant. We also found that wild-type PrP molecules are maintained in a detergent-soluble conformation throughout life in Drosophila brain neurons, whereas they become detergent-insoluble in retinal cells as flies age. PG14 protein expression in Drosophila eye did not cause retinal pathology. Our work reveals the presence of mechanisms in neurons that specifically counterbalance the production of misfolded PrP conformations, and provides an opportunity to study these processes in a model organism amenable to genetic analysis.     

Glutamate-induced suppression of inhibitory synaptic transmission in cultivated hippocampal neurons

In a dissociated culture of rat hippocampal neurons (14 to 24 daysin vitro), modulation effects of glutamate on GABA_A-ergic inhibitory transmission were studied with the use of simultaneous patch-clamp whole-cell recording from monosynaptically connected neuron pairs. In all experiments (n=49), 1.5-min-long or longer extracellular application of 0.5 to 100 μM glutamate suppressed evoked inhibitory postsynaptic currents (IPSC). This suppression usually included fast (seconds) and slow (τ=1.3 min) phases. In 83.7% of the cases studied, IPSC did not return to the control values during the entire subsequent recording period (from 10 to 64 min). When glutamate was applied in the presence of blockers of glutamate ionotropic receptors, DL-APV or CNQX, the fast phase of the effect was removed, while some suppression of inhibitory neuronal responses, although weaker, was preserved (n=19); in most cases (73.3%) this residual suppression was slow and long-lasting. It is concluded that both types of glutamate receptors, ionotropic and metabotropic, are involved in modulation of GABA_A-ergic synaptic transmission. The first above receptor type provides fast and reversible suppression, while the effect provided by the second type is slow and long-lasting.     

Inferior parietal somatosensory neurons coding face-hand coordination in Japanese macaques

Neuronal activities of the anterior part of the inferior parietal lobule (area 7b or PF) were investigated in five awake Japanese monkeys. There were neurons which had specific combinations of receptive field (RF) locations, most typically in both the face and hand; we refer to the seas Face-Hand neurons. The most interesting property of the Face-Hand neurons is that some of these neurons responded to specific behavior executed with synergism between the face (especially the mouth) and hand movements; namely, face-hand coordinated behavior (e.g., eating behavior). We call these cells Face-Hand coordination neurons (52% of all the Face-Hand neurons). These neurons discharged more strongly when the animal executed face-hand coordinated behavior, especially eating behavior, than when somatosensory stimuli were given to RFs passively, or when face movements and hand movements were executed separately. We thus propose that the neuronal activities of area 7b are related to the representation of face-hand coordination.     

BACE1 suppression by RNA interference in primary cortical neurons

Extracellular deposition of amyloid-beta (Abeta) aggregates in the brain represents one of the histopathological hallmarks of Alzheimer's disease (AD). Abeta peptides are generated from proteolysis of the amyloid precursor proteins (APPs) by beta- and gamma-secretases. Beta-secretase (BACE1) is a type I integral membrane glycoprotein that can cleave APP first to generate C-terminal 99- or 89-amino acid membrane-bound fragments containing the N terminus of Abeta peptides (betaCTF). As BACE1 cleavage is an essential step for Abeta generation, it is proposed as a key therapeutic target for treating AD. In this study, we show that small interfering RNA (siRNA) specifically targeted to BACE1 can suppress BACE1 (but not BACE2) protein expression in different cell systems. Furthermore, BACE1 siRNA reduced APP betaCTF and Abeta production in primary cortical neurons derived from both wild-type and transgenic mice harboring the Swedish APP mutant. The subcellular distribution of APP and presenilin-1 did not appear to differ in BACE1 suppressed cells. Importantly, pretreating neurons with BACE1 siRNA reduced the neurotoxicity induced by H2O2 oxidative stress. Our results indicate that BACE1 siRNA specifically impacts on beta-cleavage of APP and may be a potential therapeutic approach for treating AD.     

Optimal signal in sensory neurons under an extended rate coding concept

We define an optimal signal in parametric neuronal models on the basis of interspike interval data and rate coding schema. Under the classical approach the optimal signal is located where the frequency transfer function is steepest. Its position coincides with the inflection point of this curve. This concept is extended here by using Fisher information which is the inverse asymptotic variance of the best estimator and its dependence on the parameter value indicates accuracy of estimation. We compare the signal producing maximal Fisher information with the inflection point of the sigmoidal frequency transfer function.