Journal: bioRxiv

Article Title: NDNF+ interneurons have a privileged role in regulating cortical excitability

doi: 10.1101/2025.11.27.690945

Figure Lengend Snippet: ( A ) Cortical slice seizure model setup. ( B ) Representative LFP traces of seizure-like events (SLEs) evoked by electrical stimulation from slices expressing either hM3Dq-mCherry (purple), or mCherry only (grey) in NDNF+ neurons in baseline (Top panel) or following addition of 10 μM CNO (Bottom panel). ( C ) Seizure duration following 10 μM CNO application normalised to baseline (the unpaired mean difference between mCherry and hM3Dq groups is -0.36 [95%CI, -0.89, -0.06], p=0.19 two-sided permutation t-test, and p=0.18 Student’s t-test, mCherry n=7 slices; hM3Dq n=5 slices). ( D ) Normalised number of spikes per SLE baseline (the unpaired mean difference between mCherry and hM3Dq groups is -0.93 [95%CI, -2.44, -0.31], p=0.09 two-sided permutation t-test, and p=0.15 Student’s t-test, mCherry n=7 slices; hM3Dq n=5 slices). ( E ) Average normalised interspike interval per SLE after CNO application baseline (the unpaired mean difference between mCherry and hM3Dq groups is 0.39 [95%CI, 0.16, 0.60], p=0.01 two-sided permutation t-test, and p=0.01 Student’s t-test, mCherry n=7 slices; hM3Dq n=5 slices). ( F ) Hippocampal-entorhinal cortical slice seizure model. ( G ) Representative LFP recordings of stimulus-evoked SLEs from slices expressing hM3Dq before (top panel) and after (bottom panel) application of 10 μM CNO. ( H ) Duration of SLEs normalised to baseline (before CNO) in slices expressing mCherry only (grey; n = 8 slices) or hM3Dq-mCherry (purple; n = 6 slices). ( I ) Normalised seizure duration after CNO was decreased in hM3Dq expressing slices baseline (the unpaired mean difference between mCherry and hM3Dq groups is -0.92 [95%CI, -1.29, -0.60], p<0.001 two-sided permutation t-test, and p=0.003 Student’s t-test, mCherry n=8 slices; hM3Dq n=6 slices). ( J ) Number of spikes per SLE was decreased (the unpaired mean difference between mCherry and hM3Dq is -0.92 [95%CI, -1.36, -0.41], p=0.006 two-sided permutation t-test, and p=0.007 Student’s t-test mCherry n=8 slices; hM3Dq n=6 slices) and ( K ) interspike interval was increased in hM3Dq slices with CNO baseline (the unpaired mean difference between mCherry and hM3Dq is 0.44 [95%CI, -0.04, 1.41], p=0.19 two-sided permutation t-test, and p=0.20 Student’s t-test mCherry n=6 slices; hM3Dq n=6 slices).

Article Snippet: Recording aCSF containing the hM3Dq agonist clozapine-N-Oxide (CNO, 10 μM, Cambridge Bioscience CAY25780) was applied immediately following the 6 th stimulation.

Techniques: Expressing

Journal: bioRxiv

Article Title: NDNF+ interneurons have a privileged role in regulating cortical excitability

doi: 10.1101/2025.11.27.690945

Figure Lengend Snippet: ( A ) mCherry expression in NDNF+ neurons within the stratum lacunosum moleculare (sl-m) of the hippocampus from mice injected with either intrahippocampal saline (control) or intrahippocampal kainate (epileptic). DG = dentate gyrus. The number of mCherry-positive cells per area was unchanged in epileptic animals (the unpaired mean difference between Saline and Kainate is 26,3% [95%CI, 7.8, 50.5], p=0.072 two-sided permutation t-test, and p= 0.06 Student’s t-test, Saline n = 8 slices /3 mice; Kainate n= 20 slices /3 mice). ( B ) Experimental setup. ( C ) Representative LFP traces from hippocampal depth electrodes from a mouse expressing hM3Dq in NDNF+ neurons before and after intraperitoneal (i.p) injection of either DMSO (0.1% in saline) control or DCZ (10 μg/kg).

Article Snippet: Recording aCSF containing the hM3Dq agonist clozapine-N-Oxide (CNO, 10 μM, Cambridge Bioscience CAY25780) was applied immediately following the 6 th stimulation.

Techniques: Expressing, Injection, Saline, Control