20.5. Martina Mavrovic: Expression and functions of KCC2 in the perinatal rodent cortex

KCC2 is the main neuronal K-Cl cotransporter, which lowers the intracellular Cl- concentration and thus maintains GABAA receptor-mediated inhibition during network activity in mature neurons. Independently of its function as an ion transporter, KCC2 was shown to be necessary for the formation of excitatory synapses, where it regulates the development of dendritic spines via modulation of the actin cytoskeleton, notably cofilin phosphorylation. KCC2 expression undergoes developmental up-regulation, which parallels the rostro-caudal CNS maturation in rodents, and underlies the robust negative shift in EGABA away from the depolarizing responses characteristic of immature neurons, as well as functionally regulates the intense spino- and synaptogenesis of cortical principal neurons. These findings posit KCC2 as a key molecule for coordinating the maturation and balance of excitatory and inhibitory neurotransmission during the brain growth spurt.

While the role of KCC2 has been extensively studied during the first month of postnatal development in rodents, its functions in the perinatal cortex are only beginning to emerge. KCC2 knockout mice have altered hippocampal network activity already at embryonic day 18.5 when KCC2 is considered to be expressed at physiologically non-significant levels. Moreover, KCC2 has been found to regulate the migration of cortical interneurons by acting as a migratory stop signal in an ion transport-dependent way. On the other hand, in pyramidal neurons, KCC2-mediated ion-cotransport seems to be under kinetic suppression until around birth. Finally, the time window of the transition period of GABAergic signaling from depolarizing to hyperpolarizing, and the underlying upregulation of KCC2, coincides with the time when GABAAR modulators, notably general anesthetics, have been shown to induce lasting adverse effects on cognition and behavior in rodents. Thus far, it is not known why there is this defined time window of increased vulnerability to anesthetics, and the underlying molecular and cellular mechanisms warrant investigation.

In this Thesis, the primary goal was to study the functional significance of early KCC2 expression in the developing neocortex and hippocampus of mice and rats and to assess the effects of genetic and pharmacological modulation of KCC2 expression on the formation of cortical networks. Particular focus was put on differentiating between the ion transport-dependent and -independent roles of KCC2. This work describes a novel ion transport-independent role of KCC2 in developmental neuroapoptosis, as well as ion transport-dependent functions of KCC2 in the regulation of hippocampal network events and developmental-stage dependent vulnerability to general anesthetics.

find the cost of your paper

Sep 13, Grand Remembrances

Today is Grandparents Day in the United States. Being a Grand is a special honor. I feel very blessed that my wife and I have two grandchildren. We were able to visit them today. Yes, we are still being cautious with the coronavirus, but we also find it very difficult to not see them when they live so close. So today we did drop by to visit Jacob (age 10) and Sophia (age 7) along with their parents. We brought donuts and caught up with them. Our grandchildren are still pretty young and this is a precious time in their lives – and ours!

I wish I had known my grandparents better. We never lived in the same place. Dad was a career Air Force pilot, so we moved around a lot. But we did get to see them once in a while when they would visit us, or we them.

A Plague of Giants

There are five known magical ‘kennings’ or types: air, water, fire, earth, and plants. Each nation specializes in of these kennings, and the magic influences the society. There’s a big pitfall with this diversity of ability and locale–not everyone gets along.

Enter the Hathrim giants, or ‘lavaborn’ whose kenning is fire. Where they live the trees that fuel their fire are long gone, but the giants are definitely not welcome anywhere else. They’re big, they’re violent, and they’re ruthless. When a volcano erupts and they are forced to evacuate, they take the opportunity to relocate. They don’t care that it’s in a place where they aren’t wanted.

I first read Kevin Hearne’s Iron Druid books and loved them (also the quirky The Tales of Pell), so was curious about this new venture, starting with A PLAGUE OF GIANTS. Think Avatar: The Last Airbender meets Jim Butcher’s Codex Alera series. Elemental magic, a variety of races, different lands. And it’s all thrown at you from page one.

But this story is told a little differently. It starts at the end of the war, after a difficult victory, and a bard with earth kenning uses his magic to re-tell the story of the war to a city of refugees. And it’s this movement back and forth in time and between key players in this war that we get a singularly grand view of the war as a whole. Hearne uses this method to great effect.

There are so many interesting characters in this book that I can’t cover them all here. Often in books like this such a large cast of ‘main’ character can make the storytelling suffer, especially since they don’t have a lot of interaction with each other for the first 3/4 of the book–but it doesn’t suffer, thankfully. And the characterization is good enough, despite these short bursts, that by the end we understand these people and care about what happens to them.

If there were a main character it would be Dervan, a historian who is assigned to record (also spy on?) the bard’s stories. He finds himself caught up in machinations he feels unfit to survive. Fintan is the bard from another country, who at first is rather mysterious and his true personality is hidden by the stories he tells; it takes a while to understand him. Gorin Mogen is the leader of the Hathrim giants who decide to find a new land to settle. He’s hard to like, but as far as villains go, you understand his motivations and he can be even a little convincing. There’s Abhi, the son of hunters, who decides hunting isn’t the life for him–and unexpectedly finds himself on a quest for the sixth kenning. And Gondel Vedd, a scholar of linguistics who finds himself tasked with finding a way to communicate with a race of giants never seen before (definitely not Hathrim) and stumbles onto a mystery no one could have guessed: there may be a seventh kenning.

There are other characters, but what makes them all interesting is that they’re regular people (well, maybe not Gorin Mogen or the viceroy–he’s a piece of work) who become heroes in their own little ways, whether it’s the teenage girl who isn’t afraid to share vital information, to the scholars who suddenly find how crucial their minds are to the survival of a nation, to the humble public servants who find bravery when they need it most. This is a story of loss, love, redemption, courage, unity, and overcoming despair to not give up. All very human experiences by simple people who do extraordinary things.

Hearne’s worldbuilding is engaging. He doesn’t bottle feed you, at first it feels like drinking from a hydrant, but then you settle in and pick up things along the way. Then he shows you stuff with a punch to the gut. This is no fluffy world with simple magic without price. All the magic has a price, and more often than not it leads you straight to death’s door. For most people just the seeking of the magic will kill you. I particularly enjoyed the scenes with Ahbi and his discovery of the sixth kenning and everything associated with it. But giants? I mean, really? It isn’t bad enough fighting people who can control fire that you have to add that they’re twice the size of normal people? For Hearne if it’s war, the stakes are pretty high, and it gets ugly.

The benefit of the storytelling style is that the book, despite its length, moves along steadily (Hearne is no novice, here). The bits of story lead you along without annoying cliffhangers (mostly), and I never got bored with the switch between characters. It was easy to move between them, and they were recognizable enough that I got lost or confused. The end of the novel felt a little abrupt, but I guess that has more to do with I was ready for the story to continue, despite the exiting climax.

If you’re looking for epic fantasy with fun storytelling and clever worldbuilding, check out A PLAGUE OF GIANTS.

The post A Plague of Giants appeared first on Elitist Book Reviews.

The Artwork Of Gary Choo

Gary Choo is a concept artist/illustrator based in Singapore. I’ve know Gary for a good many years ( 17, actually ), working together in animation studios in Singapore like Silicon Illusions and Lucasfilm. Gary currently runs an art team at Mighty Bear Games, but when time allows he also draws covers for Marvel comics, and they’re amazing –

The Art Of Gary Choo
The Art Of Gary Choo
The Art Of Gary Choo
The Art Of Gary Choo
The Art Of Gary Choo

To see more of Gary’s work or to engage him for freelance work, head down to his ArtStation.

The post The Art Of Gary Choo appeared first on Halcyon Realms – Art Book Reviews – Anime, Manga, Film, Photography.

27