Neural Activity and Neurotransmission Regulate the Maturation of the Innervation Field of Cortical GABAergic Interneurons in an Age-Dependent Manner

Abstract

Neural activity guides the patterning of neuron synaptic territory in the developing nervous system. Evidence supporting this hypothesis comes from numerous studies on projection neurons in neuromuscular and visual systems. It is unknown whether the innervation field of GABAergic interneurons, which forms local dense innervations, follows similar rules.Cortical basket cells innervate hundreds of pyramidal cell somata and proximal dendrites. Thanks to this connectivity pattern, they can tightly control neural excitability and synchronization. Here we show that reducing excitation, and thus neurotransmitter release, in mouse cortical single basket cells in slice cultures decreases the number of innervated cells without changing the pattern of perisomatic innervation, both at the peak and after the proliferation phase of perisomatic synapse formation. Conversely, suppressing neurotransmitter release in single basket cells can have completely opposite effects depending on the developmental stage. Our results reveal a remarkably specific and age-dependent role of neural activity and neurotransmission levels in the establishment of the synaptic territory of cortical GABAergic cells.

Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function

“…Each PV+ basket cell innervates hundreds of neurons, with large, clustered boutons targeting the soma and the proximal dendrites of postsynaptic targets, an optimal location to control timing and frequency of action potential generation1936. Such distinct features of PV+ basket cell innervations are achieved during the first postnatal month in rodents and are modulated by neural activity levels35373839. We found that almost the totality of PV+ basket cells express SYNGAP1 in dissociated neuronal cultures (Supplementary Fig.…”

“…37) to express either the Cre recombinase together with GFP (P G67 -GFP/Cre) or GFP alone (P G67 -GFP; control basket cells) in cortical organotypic cultures prepared from Syngap1 flox/flox mice3537383940. In organotypic cultures, PV+ basket cells initially display very sparse and simple axons, which develop into complex and highly branched arbours in the following 4 weeks, recapitulating the in vivo situation3738.…”

“…In organotypic cultures, PV+ basket cells initially display very sparse and simple axons, which develop into complex and highly branched arbours in the following 4 weeks, recapitulating the in vivo situation3738. We chose to induce Syngap1 deletion in PV+ basket cells at Equivalent Postnatal day 10 (EP10=cultured prepared at Postnatal day 4+6DIV) and collect the cultures at EP24 because extensive and stereotyped maturation of PV+ basket cell innervations occurs during this time window373738394041.…”

The maturation of cortical sleep rhythms and networks over early development

“…In addition, recent work suggests that the maturation of extensive GABAergic interneuron assemblies likely plays a pivotal role in orchestrating the cortical field oscillations and network synchronization patterns observed here (Fritschy, 2008; Le Magueresse and Monyer, 2013). The selective maturation of these inhibitory circuits has been observed to occur in distinct steps over development, independent of environmental input (Ben-Ari et al, 2012; Baho and Cristo, 2012; Magueresse and Monyer, 2013). …”

Neuronal activity controls the development of interneurons in the somatosensory cortex

“…A complete blockade of GABA signaling results in over proliferation of small synapses and overgrowth of axons, demonstrating a role for GABA in the pruning of synapses during a critical period of synaptic remodeling (Wu et al, 2012). Similarly, a suppression of neurotransmitter release in single basket cells induces the formation of denser arbors and increases the number of smaller-sized boutons, without a change in the number of innervated somata (Baho and Di Cristo, 2012). In contrast, GABA signaling via the GABA-A receptor and voltage gated calcium channels induces the formation of inhibitory synapses in layer II/III pyramidal cells during early development (Oh et al, 2016).…”