Somatostatin

Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion. Somatostatin has two active forms produced by the alternative cleavage of a single preproprotein: one consisting of 14 amino acids (shown in infobox to right), the other consisting of 28 amino acids. Among the vertebrates, there exist six different somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5 and SS6. Zebrafish have all six. The six different genes, along with the five different somatostatin receptors, allow somatostatin to possess a large range of functions. Humans have only one somatostatin gene, SST. Nomenclature Synonyms of "somatostatin" include:

growth

GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons

Sean Lewis Hill, Steven Petrou, Christian Andreas Rössert, Bas-Jan Zandt

The binding of GABA (gamma-aminobutyric acid) to extrasynaptic GABA(A) receptors generates tonic inhibition that acts as a powerful modulator of cortical network activity. Despite GABA being present throughout the extracellular space of the brain, previous work has shown that GABA may differentially modulate the excitability of neuron subtypes according to variation in chloride gradient. Here, using biophysically detailed neuron models, we predict that tonic inhibition can differentially modulate the excitability of neuron subtypes according to variation in electrophysiological properties. Surprisingly, tonic inhibition increased the responsiveness (or gain) in models with features typical for somatostatin interneurons but decreased gain in models with features typical for parvalbumin interneurons. Patch-clamp recordings from cortical interneurons supported these predictions, and further in silico analysis was then performed to seek a putative mechanism underlying gain modulation. We found that gain modulation in models was dependent upon the magnitude of tonic current generated at depolarized membrane potential-a property associated with outward rectifying GABA(A) receptors. Furthermore, tonic inhibition produced two biophysical changes in models of relevance to neuronal excitability: 1) enhanced action potential repolarization via increased current flow into the dendritic compartment, and 2) reduced activation of voltage-dependent potassium channels. Finally, we show theoretically that reduced potassium channel activation selectively increases gain in models possessing action potential dynamics typical for somatostatin interneurons. Potassium channels in parvalbumin-type models deactivate rapidly and are unavailable for further modulation. These findings show that GABA can differentially modulate interneuron excitability and suggest a mechanism through which this occurs in silico via differences of intrinsic electrophysiological properties.

NATL ACAD SCIENCES2020

Parvalbumin-Expressing GABAergic Neurons in Mouse Barrel Cortex Contribute to Gating a Goal-Directed Sensorimotor Transformation

Carl Petersen, Shankar Sachidhanandam, Berat Semihcan Sermet

Sensory processing in neocortex is primarily driven by glutamatergic excitation, which is counterbalanced by GABAergic inhibition, mediated by a diversity of largely local inhibitory interneurons. Here, we trained mice to lick a reward spout in response to whisker deflection, and we recorded from genetically defined GABAergic inhibitory neurons in layer 2/3 of the primary somatosensory barrel cortex. Parvalbumin-expressing (PV), vasoactive intestinal peptide-expressing (VIP), and somatostatin-expressing (SST) neurons displayed distinct action potential firing dynamics during task performance. Whereas SST neurons fired at low rates, both PV and VIP neurons fired at high rates both spontaneously and in response to whisker stimulation. After an initial outcome-invariant early sensory response, PV neurons had lower firing rates in hit trials compared to miss trials. Optogenetic inhibition of PV neurons during this time period enhanced behavioral performance. Hence, PV neuron activity might contribute causally to gating the sensorimotor transformation of a whisker sensory stimulus into licking motor output.

Elsevier2016

GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons

Sean Lewis Hill, Steven Petrou, Christian Andreas Rössert, Bas-Jan Zandt

NATL ACAD SCIENCES2020

GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons

Parvalbumin-Expressing GABAergic Neurons in Mouse Barrel Cortex Contribute to Gating a Goal-Directed Sensorimotor Transformation

Functional characterization of selected plasmodium falciparum protein kinases

GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons

Parvalbumin-Expressing GABAergic Neurons in Mouse Barrel Cortex Contribute to Gating a Goal-Directed Sensorimotor Transformation

Functional characterization of selected plasmodium falciparum protein kinases