Daily electrical activity in the master circadian clock of a diurnal mammal
- Centre for Biological Timing, Faculty of Biology Medicine and Health, University of Manchester, United Kingdom
- Division of Neuroscience and Experimental Psychology, Faculty of Biology Medicine and Health, University of Manchester, United Kingdom
- Department of Mathematical Sciences, New Jersey Institute of Technology, United States
- Department of Quantitative Pharmacology and Pharmacometrics (QP2), United States
- Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology Medicine and Health, University of Manchester, United Kingdom
- EPSRC Centre for Predictive Modelling in Healthcare, Living Systems Institute, University of Exeter, United Kingdom
- Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, United Kingdom
Figures
Figure 1
Anatomy and neuropeptidergic organization of the Rhabdomys pumilio SCN.
(A) Coronal sections of the R. pumilio SCN taken across the rostro-caudal axis labeled with DAPI, and immunofluorescence for the main SCN neuropeptides: (B) Arginine-vasopressin (AVP), (C) …
Figure 2
Diurnal changes in the spontaneous electrical activity of Rhabdomys pumilio SCN neurons.
(A) Whole-cell patch clamp recording setup showing bright-field image of a SCN coronal brain slice. The SCN (delineated by white dotted lines) can be observed above the optic chiasm (OC), on either …
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Figure 2—source data 1
Numerical data to support graphs in Figure 2C–F.
- https://cdn.elifesciences.org/articles/68179/elife-68179-fig2-data1-v1.xlsx
Figure 3
Diverse responses to depolarizing and hyperpolarizing current pulses in Rhabdomys pumilio SCN neurons.
Representative current-clamp traces showing the different type of responses to a depolarizing pulse (1 s, +30 pA): (A) non-adapting; (B) adapting-firing; or (C) adapting-to-silent response. …
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Figure 3—source data 1
Numerical data to support graphs in Figure 3D and G.
- https://cdn.elifesciences.org/articles/68179/elife-68179-fig3-data1-v1.xlsx
Figure 4 with 4 supplements
Computational modeling of Rhabdomys pumilio SCN neurons.
(A) Schematic of conductance-based model for R. pumilio SCN neurons containing sodium (INa), calcium (ICa), potassium (IK), and leak (ILNa, ILK) currents. Orange resistors (gNa, gCa, gK) indicate …
Figure 4—figure supplement 1
Example current-clamp traces used in data assimilation algorithm for building computational models of Rhabdomys pumilio SCN neurons.
(A–F) Current-clamp recordings (blue) with the portion of the voltage trace used by the data assimilation algorithm (orange) to fit the model shown in Figure 4 and Figure 4—figure supplement 2. (A–C)…
Figure 4—figure supplement 2
Example voltage traces for a computational model of Rhabdomys pumilio SCN neurons fit using a data assimilation algorithm.
(A–F) Current-clamp recordings (black) and simulated voltage traces (red) from the model shown in Figure 4 that was fit using the portions of the data shown in Figure 4—figure supplement 1. (A–C) …
Figure 4—figure supplement 3
Ionic currents underlying action potential generation in computational models of Rhabdomys pumilio and mouse SCN neurons.
(A) Voltage trace showing spontaneous firing in model of R. pumilio SCN neurons. (a1) Magnified view of second AP shown in (A). (B) Sodium (INa, blue), calcium (ICa, magenta), potassium (IK, green), …
Figure 4—figure supplement 4
Bifurcation diagram for a computational model of Rhabdomys pumilio SCN neurons.
(A) Voltage at steady-states and maximum/minimum voltage of oscillations for the model of rebound spiking in the Type-A neuron shown in Figures 4 and 6A, and Figure 4—figure supplements 1–3 with …
Figure 5
Model simulation of the responses to depolarizing pulses in Rhabdomys pumilio SCN neurons and the underlying ionic mechanisms.
(A–B) Voltage traces of models (red) and current-clamp recordings (black) during depolarizing pulses (1 s, +30 pA) showing non-adapting (i), adapting-firing (ii), and adapting-to-silent (iii) …
Figure 6
Model simulation of the responses to hyperpolarizing pulses in Rhabdomys pumilio SCN neurons and the underlying ionic mechanisms.
(A–B) Voltage traces of models (red) and current-clamp recordings (black) during hyperpolarizing pulses (1s, -30 pA) showing rebound spiking of Type-A neurons (A) and delay responses of Type-B cells …
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Figure 6—source data 1
Numerical data to support graphs in Figure 6I.
- https://cdn.elifesciences.org/articles/68179/elife-68179-fig6-data1-v1.xlsx
Figure 7 with 1 supplement
IA conductances act to amplify extrinsic and intrinsic suppressive signals in the Rhabdomys pumilio SCN.
(A) Heatmap showing the overall effects of inhibitory (gsyn-I, red) and excitatory (gsyn-E, blue) physiological GABAergic synaptic conductances on firing frequency with increasing IA conductances in …
Figure 7—figure supplement 1
Spontaneous synaptic events in Rhabdomys pumilio SCN neurons.
Representative trace from a SCN neuron (voltage-clamped at −70 mV) showing post-synaptic currents (PSCs) under baseline conditions (top). Bath application of the GABAA receptor blocker, Bicuculline …
Author response image 1
Additional files
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Supplementary file 1
Parameter values for the computational models of Rhabdomys pumilio SCN neurons.
Models were fit to data from seven different neurons, including a non-adapting cell (Figure 5Ai), an adapting-firing cell (Figure 5Aii), an adapting-silent cell (Figure 5Aiii), two Type-A rebound spiking cells (Figures 4 and 6A), and two Type-B delay cells (Figure 6B and O). These cells were chosen for modeling because they are representative of the various responses observed across all the recordings. Each model was fit to data from six voltages traces as illustrated in Figure 4—figure supplement 1.
- https://cdn.elifesciences.org/articles/68179/elife-68179-supp1-v1.docx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/68179/elife-68179-transrepform-v1.pdf
