Cerebellum, Motor Impairment & Electrophysiology - The Snell Lab

Transcript

• 00:06We focus on the cerebellum,
• 00:08and it's this part of
• 00:09the brain that contains eighty
• 00:11percent of all the neurons
• 00:12in the brain, but it's
• 00:13small. It's in the back.
• 00:14It's actually Greek for small
• 00:15brain. And historically, it's been
• 00:17known to be responsible for
• 00:18motor coordination.
• 00:20But we know that the
• 00:21cerebellum is highly involved
• 00:23in social interaction, in cognitive
• 00:26function.
• 00:31We sit right at this
• 00:32overlap between motor impairment and
• 00:35cognitive impairment. Eighty percent of
• 00:36people with autism have some
• 00:37kind of motor impairment, and
• 00:39about fifty percent of patients
• 00:40with ADHD have some kind
• 00:42of motor impairment. So there's
• 00:43this Venn diagram, and we
• 00:44sit right in the middle
• 00:45to kind of understand how
• 00:46is the cerebellum involved in
• 00:48the motor impairment in these
• 00:50cognitive disorders, but also is
• 00:52it contributing to the cognitive
• 00:53aspects of these disorders as
• 00:55well.
• 01:01The bread and butter of
• 01:02our lab is electrophysiology.
• 01:03And so with that, we
• 01:05can actually record neuronal function.
• 01:07We have it on different
• 01:08levels. We can do electrophysiology
• 01:10in cell culture and say,
• 01:11okay. In a dish, what
• 01:12is this channel doing to
• 01:13this cell? We can do
• 01:15it in an intact brain
• 01:16and say, in a system,
• 01:17what is this mutation doing
• 01:19to this system, to the
• 01:20function of multiple cells, to
• 01:22the function of a cell
• 01:23in a brain? And so
• 01:23we're kind of going back
• 01:24and forth with that to
• 01:26compare.
• 01:28We have models of many
• 01:30of these mutations,
• 01:31and so what we can
• 01:32do with those models is
• 01:34we can record the neurons
• 01:36in those models. And so
• 01:37we use electrophysiology
• 01:39to record the function in
• 01:41health, but also record the
• 01:43function in a disease state
• 01:44and say, how do these
• 01:45mutations mess up this system?
• 01:47And then can we fix
• 01:49it by adding drugs? Can
• 01:50we fix it by manipulating
• 01:52this specific channel or channels
• 01:54that it interacts with?
• 01:57We also have a branch
• 01:59of my lab that is
• 02:00doing electrophysiology
• 02:01specifically in single cells. And
• 02:04so with that, we can
• 02:05add the DNA from these
• 02:06mutations,
• 02:07and we can say, how
• 02:08does it change the function
• 02:09of the channel? So increase,
• 02:11decrease in the channel function,
• 02:12and how is it changing
• 02:13the expression of a channel.
• 02:15And so we kind of
• 02:16have this holistic way of
• 02:17looking at these mutations
• 02:19in multiple different ways.
• 02:25Really, our goal is to
• 02:27help patients, and that's kind
• 02:28of my driving line. I
• 02:29interact with patients
• 02:30all the time. And so
• 02:32seeing them and seeing their
• 02:33passion, you just kinda wanna
• 02:34get back into the lab
• 02:35and say, okay. I'm gonna
• 02:36figure this out for you.
• 02:38Normally, with patients, they just
• 02:39kind of throw, drugs at
• 02:41them because they're treating symptoms.
• 02:42And so what we really
• 02:43wanna do is go down
• 02:44to the core. We're gonna
• 02:45go down to the mechanism
• 02:47behind these symptoms so we
• 02:49can actually treat the cause.
• 02:50And so what we're hoping
• 02:52is we can find a
• 02:53common mechanism
• 02:54that can alleviate the motor
• 02:56and alleviate some of the
• 02:57cognitive symptoms so these patients
• 02:59don't have to be on
• 03:00a laundry list of drugs.
• 03:02So we're really interested in
• 03:04understanding that, but also really
• 03:06interested in developing therapeutics based
• 03:08on the pharmacology and the
• 03:09recordings that we do to
• 03:11help fast track this to
• 03:12get it to patients.