scholarly journals Rate and timing in cortical synaptic plasticity

2002 ◽  
Vol 357 (1428) ◽  
pp. 1851-1857 ◽  
Author(s):  
Sacha B. Nelson ◽  
Per Jesper Sjöström ◽  
Gina G. Turrigiano

Debate has raged over the past few years as to whether cortical neurons transmit information primarily in their average firing rates or in the precise timing of their spikes. Here, we address the related question of which features of spike trains control plasticity at cortical synapses. Using paired recording in slices we have developed a quantitative and predictive description of the joint dependence of cortical plasticity on the rate and relative timing of pre– and postsynaptic firing. The results hold important implications for which parts of the neural code are most readily stored for later retrieval.

1999 ◽  
Vol 16 (6) ◽  
pp. 1055-1081 ◽  
Author(s):  
GEORGE J. KALARICKAL ◽  
JONATHAN A. MARSHALL

The position, size, and shape of the receptive field (RF) of some cortical neurons change dynamically, in response to artificial scotoma conditioning (Pettet & Gilbert, 1992) and to retinal lesions (Chino et al., 1992; Darian-Smith & Gilbert, 1995) in adult animals. The RF dynamics are of interest because they show how visual systems may adaptively overcome damage (from lesions, scotomas, or other failures), may enhance processing efficiency by altering RF coverage in response to visual demand, and may perform perceptual learning. This paper presents an afferent excitatory synaptic plasticity rule and a lateral inhibitory synaptic plasticity rule—the EXIN rules (Marshall, 1995)—to model persistent RF changes after artificial scotoma conditioning and retinal lesions. The EXIN model is compared to the LISSOM model (Sirosh et al., 1996) and to a neuronal adaptation model (Xing & Gerstein, 1994). The rules within each model are isolated and are analyzed independently, to elucidate their roles in adult cortical RF dynamics. Based on computer simulations, the EXIN lateral inhibitory synaptic plasticity rule and the LISSOM lateral excitatory synaptic plasticity rule produced the best fit with current neurophysiological data on visual cortical plasticity in adult animals (Chino et al., 1992; Pettet & Gilbert, 1992; Darian-Smith & Gilbert, 1995) including (1) the retinal position and shape of the expanding RFs; (2) the corticotopic direction in which responsiveness returns to the silenced cortex; (3) the direction of RF shifts; (4) the amount of change in response to blank stimuli; and (5) the lack of dynamic RF changes during conditioning with a retinal lesion in one eye and the unlesioned eye kept open, in adult animals. The effects of the LISSOM lateral inhibitory synaptic plasticity rule during artificial scotoma conditioning are in conflict with those of the other two LISSOM synaptic plasticity rules. A novel “complementary scotoma” conditioning experiment, in which stimulation of two complementary regions of visual space alternates repeatedly, is proposed to differentiate the predictions of the EXIN and LISSOM rules.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Emma M. Perkins ◽  
Karen Burr ◽  
Poulomi Banerjee ◽  
Arpan R. Mehta ◽  
Owen Dando ◽  
...  

Abstract Background Physiological disturbances in cortical network excitability and plasticity are established and widespread in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those harbouring the C9ORF72 repeat expansion (C9ORF72RE) mutation – the most common genetic impairment causal to ALS and FTD. Noting that perturbations in cortical function are evidenced pre-symptomatically, and that the cortex is associated with widespread pathology, cortical dysfunction is thought to be an early driver of neurodegenerative disease progression. However, our understanding of how altered network function manifests at the cellular and molecular level is not clear. Methods To address this we have generated cortical neurons from patient-derived iPSCs harbouring C9ORF72RE mutations, as well as from their isogenic expansion-corrected controls. We have established a model of network activity in these neurons using multi-electrode array electrophysiology. We have then mechanistically examined the physiological processes underpinning network dysfunction using a combination of patch-clamp electrophysiology, immunocytochemistry, pharmacology and transcriptomic profiling. Results We find that C9ORF72RE causes elevated network burst activity, associated with enhanced synaptic input, yet lower burst duration, attributable to impaired pre-synaptic vesicle dynamics. We also show that the C9ORF72RE is associated with impaired synaptic plasticity. Moreover, RNA-seq analysis revealed dysregulated molecular pathways impacting on synaptic function. All molecular, cellular and network deficits are rescued by CRISPR/Cas9 correction of C9ORF72RE. Our study provides a mechanistic view of the early dysregulated processes that underpin cortical network dysfunction in ALS-FTD. Conclusion These findings suggest synaptic pathophysiology is widespread in ALS-FTD and has an early and fundamental role in driving altered network function that is thought to contribute to neurodegenerative processes in these patients. The overall importance is the identification of previously unidentified defects in pre and postsynaptic compartments affecting synaptic plasticity, synaptic vesicle stores, and network propagation, which directly impact upon cortical function.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Marcelo Lopes ◽  
Angelo Karaboyas ◽  
Kazuhiko Tsuruya ◽  
Issa Al Salmi ◽  
Nidhi Sukul ◽  
...  

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) has been linked with comorbid conditions, and poorer mental and physical health-related quality-of-life (HR-QOL) in hemodialysis (HD) patients. The Skindex-10 questionnaire and a single itch-related question from the KDQOL-36 have been used to evaluate the impact of pruritus in HD patients. In this analysis, we investigated the performance of the single question and the Skindex-10 as predictors of HR-QOL in HD patients. Method We analyzed data from 4940 HD patients from 17 countries enrolled during year 2 of phase 5 of the Dialysis Outcomes and Practice Patterns Study (DOPPS, 2013): Belgium, Canada, Germany, the Gulf Cooperation Council (GCC) (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates), Italy, Japan, Russia, Spain, Sweden, Turkey, the UK, and the US. The Skindex-10 scores were calculated as per Mathur et al. (2010): responses to each of the 10 questions (0-6 scale), pertaining to how often patients were bothered by itchy skin in the past week, were summed to create a total summary score (range 0-60, with 0 indicating not at all bothered) and 3 subdomain scores [i.e., itching (disease) and its impact on mood/emotional and social functioning]. The itch-related single question from the KDQOL-36 asked: “During the past 4 weeks, to what extent were you bothered by itchy skin?” with response options including “not at all, somewhat, moderately, very much, extremely”. Itch-related measures were collected concurrently with HR-QOL measures: Physical (PCS) and Mental (MCS) Component Summary scores, derived from the SF-12. We calculated the Spearman correlation coefficient between the Skindex-10 (total score and for each of its 3 domains) and the single question. We used separate linear regression models to evaluate the predictive power of 1) the Skindex-10 score, 2) the single itch question, and 3) both, on PCS and MCS outcomes, based on R-squared values. Results Skindex-10 scores varied across countries; the proportion of patients with a very high Skindex-10 score (≥50) ranged from 12% in the GCC to only 2% in Italy, Russia and Sweden. Across all countries, 55% had a Skindex-10 score=0. For the single pruritus question, 37% answered that they were not at all bothered while 16% were very much or extremely bothered by itchy skin. The correlation between the single question and Skindex-10 was 0.71 overall, 0.72 for the disease domain, 0.62 for the social domain, and 0.70 for the emotional domain. Patient characteristics were similar across categories of both pruritus measures. Regression analyses showed that every 10 points higher in the Skindex-10 score was associated with 1.2 point lower PCS (95% CI: -1.4, -0.9) and 1.5 point lower MCS (95% CI: -1.7, -1.3) scores. Similarly, the single question showed increasingly poorer PCS and MCS scores with a greater degree of being bothered by pruritus: compared with patients not at all bothered by itchy skin, patients who were moderately bothered had 4.8 point lower PCS (-5.7, -3.9) and 4.3 point lower MCS (-5.3, -3.3) scores. The R-squared for PCS was 0.065 when using the single question and only 0.033 when using the Skindex-10 as the predictor. R-squared was also higher for MCS when using the single question (0.056) vs. Skindex-10 (0.052). When including both pruritus measures, the predictive power for PCS did not improve compared to the single question (R2=0.065), while increasing only slightly (R2=0.063) for MCS. Conclusion The single KDQOL-36 question about the extent bothered by itchy skin over the past 4 weeks was highly correlated with the Skindex-10 score and at least as predictive – if not more – of key HR-QOL measures as the Skindex-10. In daily clinical practice, utilizing 1 simple question about the extent patients are bothered by itchy skin can be a feasible and efficient way for routine assessment of pruritus to better identify HD patients with not only CKD-aP but also poorer HR-QoL.


1997 ◽  
Vol 77 (1) ◽  
pp. 217-255 ◽  
Author(s):  
L. Kaczmarek ◽  
M. Kossut ◽  
J. Skangiel-Kramska

Glutamate receptors (GluRs) provide the major excitatory input to cortical neurons. Four main subtypes of GluRs are distinguished, namely, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate, and metabotropic receptors. All of them have been implicated in neuronal plasticity, and this paper reviews data that may be pertinent to the role played by GluRs in neocortical plasticity both in adult animals as well as during postnatal development. Emphasis is given to receptor distribution analyzed by various means, such as physiological responses, ligand binding as revealed by receptor autoradiography, and expression of receptor subunits at both mRNA and protein (immunoreactivity) levels. Possible mechanisms of involvement of GluRs in plastic changes on cortical neuron response are reviewed, and data on up- and downregulation of GluRs in neocortical plasticity are summarized. Functional studies involving either activation or blocking, and effects of such manipulation on cortical plasticity are discussed.


1999 ◽  
Vol 82 (1) ◽  
pp. 188-201 ◽  
Author(s):  
Zhongzeng Li ◽  
Kendall F. Morris ◽  
David M. Baekey ◽  
Roger Shannon ◽  
Bruce G. Lindsey

This study addresses the hypothesis that multiple sensory systems, each capable of reflexly altering breathing, jointly influence neurons of the brain stem respiratory network. Carotid chemoreceptors, baroreceptors, and foot pad nociceptors were stimulated sequentially in 33 Dial-urethan–anesthetized or decerebrate vagotomized adult cats. Neuronal impulses were monitored with microelectrode arrays in the rostral and caudal ventral respiratory group (VRG), nucleus tractus solitarius (NTS), and n. raphe obscurus. Efferent phrenic nerve activity was recorded. Spike trains of 889 neurons were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Responses to stimulus protocols were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Spike-triggered averages of efferent phrenic activity and antidromic stimulation methods provided evidence for functional associations of bulbar neurons with phrenic motoneurons. Spike train cross-correlograms were calculated for 6,471 pairs of neurons. Significant correlogram features were detected for 425 pairs, including 189 primary central peaks or troughs, 156 offset peaks or troughs, and 80 pairs with multiple peaks and troughs. The results provide evidence that correlational medullary assemblies include neurons with overlapping memberships in groups responsive to different sets of sensory modalities. The data suggest and support several hypotheses concerning cooperative relationships that modulate the respiratory motor pattern. 1) Neurons responsive to a single tested modality promote or limit changes in firing rate of multimodal target neurons. 2) Multimodal neurons contribute to changes in firing rate of neurons responsive to a single tested modality. 3) Multimodal neurons may promote responses during stimulation of one modality and “limit” changes in firing rates during stimulation of another sensory modality. 4) Caudal VRG inspiratory neurons have inhibitory connections that provide negative feedback regulation of inspiratory drive and phase duration.


1985 ◽  
Vol 53 (4) ◽  
pp. 926-939 ◽  
Author(s):  
C. R. Legendy ◽  
M. Salcman

Simultaneous recordings were made from small collections (2-7) of spontaneously active single units in the striate cortex of unanesthetized cats, by means of chronically implanted electrodes. The recorded spike trains were computer scanned for bursts of spikes, and the bursts were catalogued and studied. The firing rates of the neurons ranged from 0.16 to 32 spikes/s; the mean was 8.9 spikes/s, the standard deviation 7.0 spikes/s. Bursts of spikes were assigned a quantitative measure, termed Poisson surprise (S), defined as the negative logarithm of their probability in a random (Poisson) spike train. Only bursts having S greater than 10, corresponding to an occurrence rate of about 0.01 bursts/1,000 spikes in a random spike train, were considered to be of interest. Bursts having S greater than 10 occurred at a rate of about 5-15 bursts/1,000 spikes, or about 1-5 bursts/min. The rate slightly increased with spike rate; averaging about 2 bursts/min for neurons having 3 spikes/s and about 4.5 bursts/min for neurons having 30 spikes/s. About 21% of the recorded units emitted significantly fewer bursts than the rest (below 1 burst/1,000 spikes). The percentage of these neurons was independent of spike rate. The spike rate during bursts was found to be about 3-6 times the average spike rate; about the same for longer as for shorter bursts. Bursts typically contained 10-50 spikes and lasted 0.5-2.0 s. When the number of spikes in the successively emitted bursts was listed, it was found that in some neurons these numbers were not distributed at random but were clustered around one or more preferred values. In this sense, bursts occasionally "recurred" a few times in a few minutes. The finding suggests that neurons are highly reliable. When bursts of two or more simultaneously recorded neurons were compared, the bursts often appeared to be temporally close, especially between pairs of neurons recorded by the same electrode; but bursts seldom started and ended simultaneously on two channels. Recurring bursts emitted by one neuron were occasionally accompanied by time-locked recurring bursts by other neurons.


2004 ◽  
Vol 92 (2) ◽  
pp. 959-976 ◽  
Author(s):  
Renaud Jolivet ◽  
Timothy J. Lewis ◽  
Wulfram Gerstner

We demonstrate that single-variable integrate-and-fire models can quantitatively capture the dynamics of a physiologically detailed model for fast-spiking cortical neurons. Through a systematic set of approximations, we reduce the conductance-based model to 2 variants of integrate-and-fire models. In the first variant (nonlinear integrate-and-fire model), parameters depend on the instantaneous membrane potential, whereas in the second variant, they depend on the time elapsed since the last spike [Spike Response Model (SRM)]. The direct reduction links features of the simple models to biophysical features of the full conductance-based model. To quantitatively test the predictive power of the SRM and of the nonlinear integrate-and-fire model, we compare spike trains in the simple models to those in the full conductance-based model when the models are subjected to identical randomly fluctuating input. For random current input, the simple models reproduce 70–80 percent of the spikes in the full model (with temporal precision of ±2 ms) over a wide range of firing frequencies. For random conductance injection, up to 73 percent of spikes are coincident. We also present a technique for numerically optimizing parameters in the SRM and the nonlinear integrate-and-fire model based on spike trains in the full conductance-based model. This technique can be used to tune simple models to reproduce spike trains of real neurons.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Balázs Barkóczi ◽  
Gábor Juhász ◽  
Robert G. Averkin ◽  
Imre Vörös ◽  
Petra Vertes ◽  
...  

AMPA and NMDA receptors convey fast synaptic transmission in the CNS. Their relative contribution to synaptic output and phosphorylation state regulate synaptic plasticity. The AMPA receptor subunit GluA1 is central in synaptic plasticity. Phosphorylation of GluA1 regulates channel properties and trafficking. The firing rate averaged over several hundred ms is used to monitor cellular input. However, plasticity requires the timing of spiking within a few ms; therefore, it is important to understand how phosphorylation governs these events. Here, we investigate whether the GluA1 phosphorylation (p-GluA1) alters the spiking patterns of CA1 cellsin vivo. The antidepressant Tianeptine was used for inducing p-GluA1, which resulted in enhanced AMPA-evoked spiking. By comparing the spiking patterns of AMPA-evoked activity with matched firing rates, we show that the spike-trains after Tianeptine application show characteristic features, distinguishing from spike-trains triggered by strong AMPA stimulation. The interspike-interval distributions are different between the two groups, suggesting that neuronal output may differ when new inputs are activated compared to increasing the gain of previously activated receptors. Furthermore, we also show that NMDA evokes spiking with different patterns to AMPA spike-trains. These results support the role of the modulation of NMDAR/AMPAR ratio and p-GluA1 in plasticity and temporal coding.


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