Prefrontal Cortex, Cognitive Disorders & Neurobiology - The Arnsten Lab at Yale School of Medicine

Transcript

• 00:06The prefrontal cortex is remarkable.
• 00:09It is one of the
• 00:10most recently
• 00:11evolved parts of our brain,
• 00:13and it's right behind our
• 00:14forehead.
• 00:16It has this incredible ability
• 00:19to represent
• 00:20information
• 00:21that's not actually happening,
• 00:24allowing us to think about
• 00:25things that aren't actually happening.
• 00:28And this is the foundation
• 00:30of abstract thought.
• 00:33This cortex is remarkably
• 00:36vulnerable, and we've been learning
• 00:38that it actually has built
• 00:39in mechanisms
• 00:41to take it offline, for
• 00:43example, with stress or inflammation,
• 00:45which is probably why it
• 00:47dysfunction so readily.
• 00:49So we see prefrontal deficits
• 00:51in Alzheimer's disease, Parkinson's
• 00:54disease,
• 00:54something called frontotemporal
• 00:56dementia that particularly
• 00:58targets prefrontal cortex.
• 01:01Also in disorders that affect
• 01:03younger people like schizophrenia
• 01:05and neurodevelopmental
• 01:07disorders like ADHD
• 01:09and autism.
• 01:10So figuring out why these
• 01:12circuits are so vulnerable is
• 01:14key to
• 01:16understanding the ideology of these
• 01:18disorders and coming up with
• 01:19rational treatments.
• 01:25We have been studying for
• 01:26years what makes prefrontal neurons
• 01:29so vulnerable.
• 01:30And what we found, it's
• 01:32very Shakespearean.
• 01:33The very things these neurons
• 01:36need to create
• 01:37higher cognitive operations,
• 01:40such as high levels of
• 01:41calcium,
• 01:42are the very things that
• 01:44make them vulnerable
• 01:46when they're not tightly regulated.
• 01:48So for example, stress and
• 01:50inflammation
• 01:51erode this regulation
• 01:53and leave us particularly
• 01:54vulnerable to atrophy of prefrontal
• 01:57neurons.
• 01:58So we have been studying
• 02:00this now for many years
• 02:02and use this as
• 02:04a guidepost
• 02:05for creating rational treatments to
• 02:08protect prefrontal function.
• 02:13We use a spectrum
• 02:15of techniques that go from
• 02:17the molecule all the way
• 02:18to behavior.
• 02:20So for example, one technique
• 02:22we use that's remarkable
• 02:24is something called immuno electron
• 02:26microscopy
• 02:28that lets us see molecules
• 02:30with nanometer
• 02:31resolution, so we can see
• 02:32where they are exactly
• 02:35in the synapse.
• 02:36It's very beautiful, very moving,
• 02:38and we get to see
• 02:39how mother nature has designed
• 02:42these things
• 02:46herself. We've already succeeded
• 02:49with several treatment
• 02:51translated to human use,
• 02:53but we're now at a
• 02:54point where there's
• 02:55other potential treatments that I'm
• 02:58particularly
• 02:59excited about.
• 03:00For example, we've been learning
• 03:02why prefrontal neurons are so
• 03:04vulnerable with age
• 03:06and how to protect them
• 03:07from Alzheimer's
• 03:08pathology.
• 03:09So for example, right now
• 03:11we're looking for funding to
• 03:12test a really promising treatment
• 03:15that might actually prevent
• 03:17Alzheimer's
• 03:18disease.
• 03:19We're also,
• 03:21exploring
• 03:21new stress related pathways
• 03:24and ways to protect
• 03:26the brain and especially prefrontal
• 03:28cortex from
• 03:30stress exposure,
• 03:31which may be,
• 03:33very useful in treating things
• 03:34like PTSD.
• 03:37By understanding
• 03:38the mechanism,
• 03:39we hope we can intervene
• 03:41and correct the things that
• 03:43are actively weakening
• 03:45these circuits.
• 03:47What makes it so tricky
• 03:48is these recently evolved neurons
• 03:51are totally different from classic
• 03:53neurons.
• 03:54Many of their needs are
• 03:55even opposite to those in,
• 03:57like, our sensory cortices.
• 04:00And so you need to
• 04:02respect these very unique
• 04:04mechanisms to have a rational
• 04:06strategy
• 04:07of how to protect these
• 04:09neurons.