Functional connectivity of the L2/3 VIP-to-L4 SST cell circuit motif in the primary somatosensory and visual cortices of mouse
von Jenifer Rachel
Datum der mündl. Prüfung:2023-02-23
Erschienen:2024-02-19
Betreuer:Prof. Dr. Jochen F. Staiger
Gutachter:Dr. Camin Dean
Gutachter:Prof. Dr. Dr. Oliver Schlüter
Dateien
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Diese Datei ist bis 22.02.2025 gesperrt.
Zusammenfassung
Englisch
The mammalian cortex is comprised of a multitude of cell types, wired together in intricate circuit motifs, which are recruited during different behavioral scenarios. Broadly speaking, neocortical neurons can either be defined as excitatory or inhibitory neurons, depending on the neurotransmitter they release when an action potential is conducted to the synaptic bouton. Glutamate-releasing excitatory neurons, and GABA (amino butyric acid)-releasing inhibitory neurons are present all through the cortex and form intricate connectivity motifs amongst each other to maintain the complex network activity of the cortex. One such motif is the inhibition of somatostatin (SST)-expressing neurons by vasoactive intestinal polypeptide (VIP)-expressing neurons. SST neurons are some of the most diverse inhibitory neurons in the cortex, and they can be morphologically classified into two cell types: Martinotti cells (MCs) and non-Martinotti cells (nMCs). MCs are defined by their typical axonal arbor that reaches into layer (L) 1, where it densely ramifies. On the other hand, nMCs have a locally restricted axonal arbor, ramifying intensely in the home layer. In the primary somatosensory cortex (S1), MCs are almost exclusively the type of SST neuron found in L2/3, L5b and L6, while nMCs are found exclusively in L4 and L5a. In sharp contrast, in the primary visual cortex (V1), studies have reported that the vast majority of L4 SST neurons are MCs. VIP neurons have been shown to preferentially target SST neurons, thereby lifting the inhibition of SSTs onto excitatory neurons. This ‘inhibition of inhibition’ is widely referred to as ‘disinhibition’, and the VIP-to-SST disinhibitory motif is one of the most well studied disinhibitory motifs across L2/3 of sensory and association areas of the mouse cortex. However, due to the heavy occurrence of MCs in L2/3, these studies have described the VIP-to-MC motif quite well, but the VIP-to-nMC motif is yet to be described. Furthermore, while several studies have focused on identifying the intralaminar impact of VIP neurons (i.e, within L2/3), not many have tried to shed light on the translaminar inhibition effected by VIP neurons. Most VIP somas are localized in L2/3 (~60%), however, they extend their axon vertically, in a narrow columnar projection through all the layers of the cortex, thereby being well-placed to extend inhibition onto the entire cortical column. Keeping in mind the different morphological subtypes of SST neurons present in L4 of S1 and V1 cortices, we wanted to study not just the translaminar effect of L2/3 VIP neurons, but also identify the VIP-to-nMC and VIP-to MC motifs in two different cortical sensory areas. Firstly, we studied the morphological and electrophysiological properties of L4 SST neurons in S1 and V1 cortices by means of whole-cell patch clamp electrophysiology followed by morphological reconstructions. In line with previous reports, we identified that the majority of SST neurons in L4 of S1 were nMCs, while L4 of V1 was populated by MCs. However, the electrophysiological properties of both SST subtypes were invariant across cortices. Secondly, we used paired whole-cell patch clamp electrophysiology to study the connectivity properties of L2/3 VIP neurons into L4 SST neurons in S1 and V1. Around 40-45% of tested SST cells were inhibited by VIP neurons in both cortices. Unitary synaptic properties of the VIP-to-nMC and VIP-to MC motifs were similar. We also studied the frequency-mediated differences in VIP inhibition onto nMCs and MCs. Here, we found strong differences in VIP-evoked responses onto SST neurons in both cortices. While we identified a subset of neurons in both cortices that responded to stimulation of VIP neurons at 50 Hz with short-term facilitation, we also found some SST neurons showing no appreciable form of short-term plasticity at any tested frequency. Crucially, in S1 but not in V1, we found a strong subset of SST neurons that responded to VIP stimulation at all frequencies, but especially at high frequency with strong short-term depression. We hypothesize that the differences in the functional embedding of the two motifs might be related to the reported differences in top-down inputs received by L4 neurons in both sensory areas. To summarize, we identify that the VIP-to-SST motif is present and hard-wired across two sensory areas of the mouse cortex. However, the recruitment of nMCs and MCs by temporally mediated activity of VIP neurons is starkly different, leading to the establishment of cortical area-specific and cell type-specific feedback disinhibitory motifs.
Keywords: somatosensory cortex; visual cortex; vasoactive intestinal polypeptide; somatostatin; Martinotti cell; non-Martinotti cell; plasticity; short-term facilitation; short-term depression