Sleep down state-active ID2/Nkx2.1 interneurons in the neocortex

Abstract

Extended Data Fig. 2 Network property statistics of DSA interneurons (A) Statistical contrast matrices (two-sided Tukey's test) for firing rates of pyramidal cells (PYR), interneurons (INT) and DSA interneurons during waking quiescence (QWake), NREM sleep, REM sleep and active behavior (Walk). (B) Same layout and statistical comparisons as in A but for the average unit CCGs as a function of brain state. (C) Pearson correlations (tested using a Student's t distribution) between average CCG responses of NREM sleep, QWake, REM sleep and walking behavior for all groups. Note that spike vs population relationships are preserved across brain states. (D) Top: Average joint Z-score rate density between 10% of the interneurons (100 shufflings), 90% remaining interneurons and pyramidal cells neurons (left) and between 10% of the pyramidal cells (100 shufflings), interneurons and remaining pyramidal neurons. Bottom: Spearman correlation and statistical contrast matrices (two-sided Tukey's test) for interneuron and pyramidal neurons rate and Z-scored population for all shown joint histograms. (E) Average (mean ± IC95) partial correlation values of the Z-scored rate for all groups (blue for ρDSA,INT controlling for PYR; red for ρDSA,PYR controlling for INT; magenta for ρPYR,INT controlling for DSA), after truncating high firing rate units to match median the spikes number of pyramidal cells (average from n = 32 sessions, P < 10 -25 , F(2, 2787) = 57.42, repeated measures ANOVA). (F) Left: distribution of excitatory divergence in all groups. Only putative pyramidal units excited their postsynaptic target cells (incidence probability for all groups in top-inset; P < 10 -110 , χ 2 (2) = 504.24, χ 2 test). Right: distribution of excitatory convergence for all cell groups (P < 10 -67 , χ 2 (2) = 306.15, χ 2 test). DSA neurons have fewer excitatory connections than the interneurons group (P < 10 -4 , χ 2 (1) = 11.36, χ 2 test). ***P<0.001. Extended Data Fig. 3 Mechanisms of DSA neuron firing during DOWN states -model results (A) Spiking neural model containing 100 leaky DSA neurons receiving an asymmetric inhibitory/excitatory drive (top-left scheme). Bottom, UP/DOWN transitions with DOWN-selective firing DSA neurons (gray dots in the rastergram at the top). Top right, log firing rate distributions in the model corresponded to the those of the recorded neurons. (B) Peri-DOWN-state Z scored firing raster plot for all simulated principal cells (PYR, left) and

NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain

“…Nkx2.1 protein is established to be expressed in cycling-MGE progenitors around ∼ED10.5 and it is thought to be turned-off in the postnatal cortex. However, it was recently indicated that subsets of late-born axo-axonic interneurons (He et al, 2016), and subsets of NGFC interneurons (Valero et al, 2021) interneuron subsets that express Nkx2-1 gene appeared to be having increased cell recoveries in our scRNAseq assay, we examined the expression of Nkx2-1 protein in the postnatal brain with a verified antibody. First, anti-Nkx2-1 immunostaining revealed a clear expression of putative-nuclear staining in the cortex and the hippocampus, albeit at a lesser density than in the adjacent striatum on saggital sections.…”

Metal microdrive and head cap system for silicon probe recovery in freely moving rodent

“…This enabled bilateral silicon probe implantation in the CA1 region of the hippocampus of rats ( Rogers et al, 2021 ). Reduced weight allowed us to use the same drive in mice ( Valero et al, 2021 ) and rats. (Note, that the shorter mouse microdrive is not supported anymore).…”

Development, Diversity, and Death of MGE-Derived Cortical Interneurons

“…Supragranular PV + INs receive inputs from excitatory corticocortical affer-ents as well as from neighbouring pyramidal neurons (Figure 4) [149,[204][205][206], indicating that PV + INs not only provide feedforward but also feedback inhibition, preferentially targeting the proximal dendrites and the soma of pyramidal neurons. PV + INs are known to innervate Chandelier cells, VIP + , CCK + , nNOS + , and SOM + INs [194,207,208]. In contrast, SOM + INs mostly receive excitatory inputs from neighbouring pyramidal neurons and weaker inputs from thalamic and corticocortical afferents, in turn preferentially inhibiting the distal and proximal dendrites of not only pyramidal cells but also PV + , nNOS + , and VIP + INs (Figure 4) [192,193,[208][209][210][211][212][213].…”

“…PV + INs are known to innervate Chandelier cells, VIP + , CCK + , nNOS + , and SOM + INs [194,207,208]. In contrast, SOM + INs mostly receive excitatory inputs from neighbouring pyramidal neurons and weaker inputs from thalamic and corticocortical afferents, in turn preferentially inhibiting the distal and proximal dendrites of not only pyramidal cells but also PV + , nNOS + , and VIP + INs (Figure 4) [192,193,[208][209][210][211][212][213]. It is postulated that SOM + INs are "ideally located within the cortical circuit to modulate sensory integration" [214] Selective inactivation of PV + INs results in working memory impairments, cognitive deficits, and reduced behavioural flexibility and sociability in mice [238][239][240].…”