scholarly journals Cyclic AMP reverses the effects of aging on pacemaker activity and If in sinoatrial node myocytes

2017 ◽  
Vol 149 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Emily J. Sharpe ◽  
Eric D. Larson ◽  
Catherine Proenza
Keyword(s):  
Cyclic Amp ◽  
Firing Rate ◽  
Sinoatrial Node ◽  
Voltage Dependence ◽  
Pacemaker Activity ◽  
Firing Rates ◽  
Aged Mice ◽  
Age Dependent ◽  
Effects Of Aging ◽  
Hyperpolarizing Shift

Aerobic capacity decreases with age, in part because of an age-dependent decline in maximum heart rate (mHR) and a reduction in the intrinsic pacemaker activity of the sinoatrial node of the heart. Isolated sinoatrial node myocytes (SAMs) from aged mice have slower spontaneous action potential (AP) firing rates and a hyperpolarizing shift in the voltage dependence of activation of the “funny current,” If. Cyclic AMP (cAMP) is a critical modulator of both AP firing rate and If in SAMs. Here, we test the ability of endogenous and exogenous cAMP to overcome age-dependent changes in acutely isolated murine SAMs. We found that maximal stimulation of endogenous cAMP with 3-isobutyl-1-methylxanthine (IBMX) and forskolin significantly increased AP firing rate and depolarized the voltage dependence of activation of If in SAMs from both young and aged mice. However, these changes were insufficient to overcome the deficits in aged SAMs, and significant age-dependent differences in AP firing rate and If persisted in the presence of IBMX and forskolin. In contrast, the effects of aging on SAMs were completely abolished by a high concentration of exogenous cAMP, which restored AP firing rate and If activation to youthful levels in cells from aged animals. Interestingly, the age-dependent differences in AP firing rates and If were similar in whole-cell and perforated-patch recordings, and the hyperpolarizing shift in If persisted in excised inside-out patches, suggesting a limited role for cAMP in causing these changes. Collectively, the data indicate that aging does not impose an absolute limit on pacemaker activity and that it does not act by simply reducing the concentration of freely diffusible cAMP in SAMs.

scholarly journals Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

2013 ◽  
Vol 110 (44) ◽  
pp. 18011-18016 ◽  
Author(s):  
E. D. Larson ◽  
J. R. St. Clair ◽  
W. A. Sumner ◽  
R. A. Bannister ◽  
C. Proenza
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Pacemaker Activity ◽  
Maximum Heart Rate ◽  
Age Dependent

scholarly journals A deep convolutional visual encoding model of neuronal responses in the LGN

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Eslam Mounier ◽  
Bassem Abdullah ◽  
Hani Mahdi ◽  
Seif Eldawlatly
Keyword(s):  
Firing Rate ◽  
Visual Information ◽  
Visual Stimulation ◽  
Neuronal Population ◽  
Neuronal Firing ◽  
Electrode Arrays ◽  
Deep Convolutional Neural Networks ◽  
Firing Rates ◽  
Spatiotemporal Representation

AbstractThe Lateral Geniculate Nucleus (LGN) represents one of the major processing sites along the visual pathway. Despite its crucial role in processing visual information and its utility as one target for recently developed visual prostheses, it is much less studied compared to the retina and the visual cortex. In this paper, we introduce a deep learning encoder to predict LGN neuronal firing in response to different visual stimulation patterns. The encoder comprises a deep Convolutional Neural Network (CNN) that incorporates visual stimulus spatiotemporal representation in addition to LGN neuronal firing history to predict the response of LGN neurons. Extracellular activity was recorded in vivo using multi-electrode arrays from single units in the LGN in 12 anesthetized rats with a total neuronal population of 150 units. Neural activity was recorded in response to single-pixel, checkerboard and geometrical shapes visual stimulation patterns. Extracted firing rates and the corresponding stimulation patterns were used to train the model. The performance of the model was assessed using different testing data sets and different firing rate windows. An overall mean correlation coefficient between the actual and the predicted firing rates of 0.57 and 0.7 was achieved for the 10 ms and the 50 ms firing rate windows, respectively. Results demonstrate that the model is robust to variability in the spatiotemporal properties of the recorded neurons outperforming other examined models including the state-of-the-art Generalized Linear Model (GLM). The results indicate the potential of deep convolutional neural networks as viable models of LGN firing.

Encoding timing and intensity in the ventral cochlear nucleus of the cat

1986 ◽  
Vol 56 (2) ◽  
pp. 261-286 ◽  
Author(s):  
W. S. Rhode ◽  
P. H. Smith
Keyword(s):  
Firing Rate ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Cell Types ◽  
Nerve Fibers ◽  
Frequency Selectivity ◽  
Firing Rates ◽  
Ventral Cochlear Nucleus ◽  
Auditory Nerve Fibers ◽  
Different Cell Types

Physiological response properties of neurons in the ventral cochlear nucleus have a variety of features that are substantially different from the stereotypical auditory nerve responses that serve as the principal source of activation for these neurons. These emergent features are the result of the varying distribution of auditory nerve inputs on the soma and dendrites of the various cell types within the nucleus; the intrinsic membrane characteristics of the various cell types causing different responses to the same input in different cell types; and secondary excitatory and inhibitory inputs to different cell types. Well-isolated units were recorded with high-impedance glass microelectrodes, both intracellularly and extracellularly. Units were characterized by their temporal response to short tones, rate vs. intensity relation, and response areas. The principal response patterns were onset, chopper, and primary-like. Onset units are characterized by a well-timed first spike in response to tones at the characteristic frequency. For frequencies less than 1 kHz, onset units can entrain to the stimulus frequency with greater precision than their auditory nerve inputs. This implies that onset units receive converging inputs from a number of auditory nerve fibers. Onset units are divided into three subcategories, OC, OL, and OI. OC units have extraordinarily wide dynamic ranges and low-frequency selectivity. Some are capable of sustaining firing rates of 800 spikes/s at high intensities. They have the smallest standard deviation and coefficient of variation of the first spike latency of any cells in the cochlear nuclei. OC units are candidates for encoding intensity. OI and OL units differ from OC units in that they have dynamic ranges and frequency selectivity ranges much like those of auditory nerve fibers. They differ from one another in their steady-state firing rates; OI units fire mainly at the onset of a tone. OI units also differ from OL units in that they prefer frequency sweeps in the low to high direction. Primary-like-with-notch (PLN) units also respond to tones with a well-timed first spike. They differ from onset cells in that the onset peak is not always as precise as the spontaneous rate is higher. A comparison of spontaneous firing rate and saturation firing rate of PLN units with auditory nerve fibers suggest that PLN units receive one to four auditory nerve fiber inputs. Chopper units fire in a sustained regular manner when they are excited by sound.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional Properties of Single Motor Units in the Inferior Head of Human Lateral Pterygoid Muscle: Task Firing Rates

2002 ◽  
Vol 88 (2) ◽  
pp. 751-760 ◽  
Author(s):  
I. Phanachet ◽  
T. Whittle ◽  
K. Wanigaratne ◽  
G. M. Murray
Keyword(s):  
Firing Rate ◽  
Correlation Coefficients ◽  
Motor Units ◽  
Lateral Pterygoid Muscle ◽  
Jaw Movements ◽  
Firing Rates ◽  
Single Motor ◽  
Single Motor Units ◽  
Fine Control ◽  
Contralateral Movement

The precise function of the inferior head of the human lateral pterygoid muscle (IHLP) is unclear. The aim of this study was to clarify the normal function of the IHLP. The hypothesis was that an important function of the IHLP is the generation and fine control of horizontal (i.e., anteroposterior and mediolateral) jaw movements. The activities of 50 single motor units (SMUs) were recorded from IHLP (14 subjects) during two- or three-step contralateral movement ( n = 36) and/or protrusion ( n = 33). Most recording sites were identified by computer tomography. There was a statistically significant overall increase in firing rate as the magnitude of jaw displacement increased between the holding phases (range of increments: 0.3–1.6 mm). The firing rates during the dynamic phases for each unit were significantly greater than those during the previous holding phases but less than those during the subsequent holding phases. For the contralateral step task at the intermediate rate, the cross-correlation coefficients between jaw displacement in the mediolateral axis and the mean firing rate of each unit ranged from r = 0.29 to 0.77; mean ± SD; r = 0.49 ± 0.13 (protrusive step task: r = 0.12–0.74, r = 0.44 ± 0.14 for correlation with anterior–posterior axis). The correlation coefficients at the fast rate during the contralateral step task and the protrusive step task were significantly higher than those at the slow rate. The firing rate change of the SMUs per unit displacement between holding phases was significantly greater for the lower-threshold than for the higher-threshold units during contralateral movement and protrusion. After dividing IHLP into four regions, the SMUs recorded in the superior part exhibited significantly greater mean firing rate changes per unit displacement during protrusion than for the SMUs recorded in the inferior part. Significantly fewer units were related to the protrusive task in the superior–medial part. These data support previously proposed notions of functional heterogeneity within IHLP. The present findings provide further evidence for an involvement of the IHLP in the generation and fine control of horizontal jaw movements.

scholarly journals Multimodal Medullary Neurons and Correlational Linkages of the Respiratory Network

1999 ◽  
Vol 82 (1) ◽  
pp. 188-201 ◽  
Author(s):  
Zhongzeng Li ◽  
Kendall F. Morris ◽  
David M. Baekey ◽  
Roger Shannon ◽  
Bruce G. Lindsey
Keyword(s):  
Firing Rate ◽  
Nucleus Tractus Solitarius ◽  
Motor Pattern ◽  
Sensory Modality ◽  
Spike Trains ◽  
Negative Feedback Regulation ◽  
Firing Rates ◽  
Respiratory Network ◽  
Cross Correlation Analysis ◽  
Stimulation Of

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.

Quantitative Analysis of Abducens Neuron Discharge Dynamics During Saccadic and Slow Eye Movements

1999 ◽  
Vol 82 (5) ◽  
pp. 2612-2632 ◽  
Author(s):  
Pierre A. Sylvestre ◽  
Kathleen E. Cullen
Keyword(s):  
Eye Movements ◽  
Firing Rate ◽  
Eye Movement ◽  
Neuronal Activity ◽  
Smooth Pursuit ◽  
Slow Phase ◽  
Vestibular Nystagmus ◽  
Firing Rates ◽  
Rapid Eye Movements ◽  
Eye Velocity

The mechanics of the eyeball and its surrounding tissues, which together form the oculomotor plant, have been shown to be the same for smooth pursuit and saccadic eye movements. Hence it was postulated that similar signals would be carried by motoneurons during slow and rapid eye movements. In the present study, we directly addressed this proposal by determining which eye movement–based models best describe the discharge dynamics of primate abducens neurons during a variety of eye movement behaviors. We first characterized abducens neuron spike trains, as has been classically done, during fixation and sinusoidal smooth pursuit. We then systematically analyzed the discharge dynamics of abducens neurons during and following saccades, during step-ramp pursuit and during high velocity slow-phase vestibular nystagmus. We found that the commonly utilized first-order description of abducens neuron firing rates (FR = b + kE + rE˙, where FR is firing rate, E and E˙ are eye position and velocity, respectively, and b, k, and r are constants) provided an adequate model of neuronal activity during saccades, smooth pursuit, and slow phase vestibular nystagmus. However, the use of a second-order model, which included an exponentially decaying term or “slide” (FR = b + kE + rE˙ + uË − c[Formula: see text]), notably improved our ability to describe neuronal activity when the eye was moving and also enabled us to model abducens neuron discharges during the postsaccadic interval. We also found that, for a given model, a single set of parameters could not be used to describe neuronal firing rates during both slow and rapid eye movements. Specifically, the eye velocity and position coefficients ( r and k in the above models, respectively) consistently decreased as a function of the mean (and peak) eye velocity that was generated. In contrast, the bias ( b, firing rate when looking straight ahead) invariably increased with eye velocity. Although these trends are likely to reflect, in part, nonlinearities that are intrinsic to the extraocular muscles, we propose that these results can also be explained by considering the time-varying resistance to movement that is generated by the antagonist muscle. We conclude that to create realistic and meaningful models of the neural control of horizontal eye movements, it is essential to consider the activation of the antagonist, as well as agonist motoneuron pools.

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