NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal’s behavioral state

The organization and development of cortical interneuron presynaptic circuits are area specific

“…Retrogradely labeled neurons were defined using anatomical atlas alignment and the degree of connectivity from the neurons retrogradely labeled in each brain structure was normalized in accordance with the total number of retrogradely labeled neurons, as previously described (A ¨hrlund-Richter et al, 2019;Cohen-Kashi Malina et al, 2021;Wall et al, 2016) (Figures 1B and 1E; STAR Methods; N = 21 total adult control animals: N = 11/10 PV/SST cINs; N = 3-4 per cell type within each area and N = 20 total P10 control animals; N = 9/11 PV/SST cINs; n = 3-4 per cell type within each area).…”

“…To compare areal, cell-type, and developmental connectivity, we measured the degree of connectivity as the number of retrogradely labeled neurons in each brain structure normalized to the total number of retrogradely labeled neurons in each brain as previously reported (A ¨hrlund- Richter et al, 2019;Cohen-Kashi Malina et al, 2021;Wall et al, 2016). This allows the aggregate changes across regions to be reflected in a single measure, reflecting the dynamic alterations in connectivity across development.…”

Mechanism and consequence of daily modulation of cortical parvalbumin-positive inhibitory neurons

“…For example, it has been shown that nAChR activation selectively potentiates the thalamocortical but not the intracortical synapses of L3 pyramidal neurons in the primary somatosensory cortex(Gil, Connors et al, 1997). A recent study reported that the NDNF interneurons in V1 L1 specifically target supragranular PV neurons(Cohen-Kashi Malina, Tsivourakis et al, 2021), which could be another explanation for the selectivity of ACh. On the other hand, we have not examined other neuromodulators such as serotonin and histamine, both of which have dense innervation in the visual cortex and also show rhythmic brain levels(Kosofsky, Molliver et al, 1984, Manning, Wilson et al, 1996).…”

Dynamic interplay between thalamic activity and Cajal-Retzius cells regulates the wiring of cortical layer 1

“…The mature architecture of the neocortex enables circuits to integrate bottom-up thalamic sensory information with top-down information that provides context, value, and feedback from internal representations ( Harris and Shepherd, 2015 ; Keller and Mrsic-Flogel, 2018 ; Schuman et al., 2021 ). Anatomically, layer 1 (L1), the most superficial layer of the neocortex, has emerged as a major site for top-down modulation ( Cauller, 1995 ; Cruikshank et al., 2012 ; Ibrahim et al., 2021 ; Schuman et al., 2021 ), with axonal inputs targeting apical dendrites of both upper and deep cortical layers ( Abs et al., 2018 ; Cruikshank et al., 2012 ; Gambino et al., 2014 ; Hartung and Letzkus, 2021 ; Schuman et al., 2021 ; Williams and Holtmaat, 2019 ) as well as GABAergic interneurons, together contributing to regulate the excitation/inhibition (E/I) balance ( Anastasiades et al., 2021 ; Cohen-Kashi Malina et al., 2021 ; Fan et al., 2020 ; Genescu and Garel, 2021 ; Gesuita and Karayannis, 2021 ; Hartung and Letzkus, 2021 ; Ibrahim et al., 2016 , 2020 , 2021 ). Increasing evidence points toward a role of L1 in integrating top-down inputs, with the bottom-up thalamic inputs driven by external stimulation ( Cauller, 1995 ; Schuman et al., 2021 ).…”