Fig. 7: POMCLepr+ and POMCGlp1r+ neurons have distinct intrinsic electrophysiological properties. | Nature Neuroscience

Fig. 7: POMCLepr+ and POMCGlp1r+ neurons have distinct intrinsic electrophysiological properties.

From: Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting

Fig. 7

a, Membrane potential (EM ) of POMCLepr+ and POMCGlp1r+ neurons (POMCLepr+, n = 38, EM = −66.72 ± 0.20 mV; POMCGlp1r+, n = 39, EM = −61.20 ± 1.29 mV; PMW = 0.001, U = 418). b,c, Input resistance. b, Mean response to 5-pA hyperpolarizing current pulses (POMCLepr+, n = 37; POMCGlp1r+, n = 28) and violin plots (c) showing the input resistance of POMCLepr+ and POMCGlp1r+ neurons (POMCLepr+, n = 37, Ri = −1.24 ± 0.09 GΩ; POMCGlp1r+, n = 28, Ri = −1.61 ± 0.12GΩ; PMW = 0.022, U = 345). d,e, Excitability I. Original recording illustrating a depolarizing ascending (asc.) and descending (desc.) current ramp protocol in POMCLepr+ and POMCGlp1r+ neurons (d) and respective spike-number ratios of the ascending and descending phase of the protocol in POMCLepr+ and POMCGlp1r+ neurons (e; 10 pA: POMCLepr+, n = 24, r = 2.33 ± 0.45; POMCGlp1r+, n = 18, r = 3.35 ± 0.33; PMW = 0.0019, U = 96.5, 15 pA: POMCLepr+, n = 29, r = 2.81 ± 0.54; POMCGlp1r+, n = 23, r = 3.64 ± 0.58; PMW = 0.0033, U = 176.5; 20 pA: POMCLepr+, n = 31, r = 3.06 ± 0.55; POMCGlp1r+, n = 24, r = 3.34 ± 0.56; PMW = 0.024, U = 239.5; 25 pA: POMCLepr+, n = 32, r = 3.28 ± 0.59; POMCGlp1r+, n = 23, r = 3.41 ± 0.68; PMW = 0.0527, U = 245.5). f–h, Excitability II. Example responses to 30-pA pulses (f). Number of action potentials (APs) as a function of current pulse amplitude (pA; g; POMCLepr+, n = 32, slope = 0.687 ± 0.073 (AP/pA); POMCGlp1r+, n = 26, slope = 0.817 ± 0.096 (AP/pA); PF = 0.0322, F = 4.62) in POMCLepr+ and POMCGlp1r+ neurons and the respective slopes (h). i,j, Post-inhibitory rebound excitation. Original recordings illustrating the responses to a depolarizing current pulse that followed a prolonged (2 s) hyperpolarizing pre-pulse (i). Mean maximal instantaneous frequency as a function of the pre-pulse potential for POMCLepr+ and POMCGlp1r+ neurons (j; −120mV: POMCLepr+, n = 32, fmax = 14.93 ± 2.97 Hz; POMCGlp1r+, n = 23, fmax = 29.12 ± 7.14 Hz; PMW = 0.0773, U = 264. −110 mV: POMCLepr+, n = 32, fmax = 15.04 ± 2.70 Hz; POMCGlp1r+, n = 23, fmax = 29.83 ± 7.16 Hz; PMW = 0.0374, U = 246. −100 mV: POMCLepr+, n = 32, fmax = 15.29 ± 2.90 Hz; POMCGlp1r+, n = 23, fmax = 31.10 ± 6.38 Hz; PMW = 0.0044, U = 203. −90 mV: POMCLepr+, n = 32, fmax = 14.05 ± 2.53 Hz; POMCGlp1r+, n = 23, fmax = 29.75 ± 6.91 Hz; PMW = 0.0374, U = 246. −80 mV: POMCLepr+, n = 32, fmax = 11.48 ± 1.78 Hz; POMCGlp1r+, n = 22, fmax = 22.14 ± 4.54 Hz; PMW = 0.017, U = 217. −70 mV: POMCLepr+, n = 29, fmax = 7.46 ± 0.54 Hz; POMCGlp1r+, n = 19, fmax = 10.25 ± 1.46 Hz; PMW = 0.2081, U = 215). k,l, Sag potentials during hyperpolarization. Original recordings illustrating the response to five consecutive hyperpolarizing current pulses adjusted to reach −120 mV (k). Violin plots illustrating the sag amplitudes at hyperpolarization to −120mV (l; POMCLepr+, n = 37, EM = −7.46 ± 0.50 mV; POMCGlp1r+, n = 28, EM = −5.69 ± 0.55 mV; PMW = 0.0057, U = 311). m,n, SFA. m, Original traces illustrating the first 5 s of a response to a 10-s depolarizing current pulse in POMCLepr+ and POMCGlp1r+ neurons. Violin plot showing SFA ratios (n) of POMCLepr+ and POMCGlp1r+ neurons (POMCLepr+, n = 30, r = 3.6 ± 0.35; POMCGlp1r+, n = 24, r = 4.66 ± 0.44; PMW = 0.0233, U = 230). o–q, Afterhyperpolarization (AHP) and afterdepolarization (ADP). o, Original traces illustrating the slow AHP after 1-s depolarizing stimuli in POMCLepr+ and POMCGlp1r+ neurons, and the ADP in POMCLepr+ neurons. p, AHP amplitude for POMCLepr+ and POMCGlp1r+ neurons as a function of the stimulus amplitude (5 pA, POMCLepr+, n = 32, ΔEM = −1.36 ± 0.19 mV; POMCGlp1r+, n = 26, ΔEM = −1.97 ± 0.30 mV; PuT = 0.084, t = 1.76, df = 56. 10 pA: POMCLepr+, n = 32, ΔEM = −0.77 ± 0.44 mV; POMCGlp1r+, n = 26, ΔEM = −2.20 ± 0.36 mV; PMW = 0.0156, U = 262. 15 pA: POMCLepr+, n = 32, ΔEM = −1.36 ± 0.50 mV; POMCGlp1r+, n = 26, ΔEM = −3.28 ± 0.51 mV; PuT = 0.0098, t = 2.675, df = 56. 20 pA: POMCLepr+, n = 32, ΔEM = −2.01 ± 0.48 mV; POMCGlp1r+, n = 26, ΔEM = −4.38 ± 0.57 mV; PMW= 0.0044, U = 236. 25 pA: POMCLepr+, n = 32, ΔEM = −3.13 ± 0.53 mV; POMCGlp1r+, n = 26, ΔEM = −4.82 ± 0.63 mV; PuT = 0.0438, t = 2.06, df = 56. 30 pA: POMCLepr+, n = 32, ΔEM = −4.06 ± 0.63 mV; POMCGlp1r+, n = 26, ΔEM = −5.82 ± 0.72 mV; PuT = 0.0688, t = 1.86, df = 56. 35 pA: POMCLepr+, n = 32, ΔEM = −4.34 ± 0.59 mV; POMCGlp1r+, n = 26, ΔEM = −6.60 ± 0.66 mV; PuT = 0.0131, t = 2.56, df = 56. 40 pA: POMCLepr+, n = 32, ΔEM = −5.07 ± 0.55 mV; POMCGlp1r+, n = 26, ΔEM = −6.86 ± 0.68 mV; PuT = 0.043, t = 2.07, df = 56. 45 pA: POMCLepr+, n = 32, ΔEM = −5.58 ± 0.67 mV; POMCGlp1r+, n = 26, ΔEM = −7.49 ± 0.73 mV; PMW = 0.0659, U = 298. 50 pA: POMCLepr+, n = 32, ΔEM = −6.29 ± 0.67 mV; POMCGlp1r+, n = 25, ΔEM = −7.66 ± 0.78 mV; PMW = 0.3579, U = 342). Inset shows amplitude of the ADP, which was predominantly observed in POMCLepr+ neurons. q, Percentage of POMCLepr+ and POMCGlp1r+ neurons revealing ADPs after the 1-s excitatory stimuli (POMCLepr+ n = 32; POMCGlp1r+ n = 26). r–t, Action potential waveform of POMCLepr+ and POMCGlp1r+ neurons. Mean action potential phase plots; the region of the dashed rectangle is shown in higher resolution on the right (r). Action potential threshold, defined as when the rate in change of EM reaches 10 mV/ms (s; POMCLepr+, n = 33, EM = −43.82 ± 0.43 mV; POMCGlp1r+, n = 30, EM = −42.28 ± 0.55 mV; PMW = 0.0212, U = 328) and depolarization rate (t; POMCLepr+, n = 33, DR = −380.6 ± 14.5 mV/ms; POMCGlp1r+, n = 30, DR = −320.5 ± 15.6 mV/ms; PuT = 0.0064, t = 2.83, df = 61). In all recordings, synaptic input was pharmacologically blocked (Methods). Error bars show ± s.e.m. ***P < 0.001; **P < 0.01; *P < 0.05. Bold lines in violin plots mark the median and light lines represent quartiles. n, number of cells recorded. DR, depolarization rate; r, ratio.

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