Neuroscientist Gains Insights Into Human Brain From Study
of Marine Snail
December 7, 2004
Contact: Stuart Wolpert ( firstname.lastname@example.org )
What can cellular neuroscientists learn
about the human brain from studying a marine snail? Much
more than one might suspect.
"On a cell biological level, the mechanisms
of learning and memory are identical, as far as we can
tell," said David Glanzman, a UCLA professor of physiological
science and neurobiology, whose research has strengthened
the view that the human brain and that of a snail named
Aplysia are surprisingly similar. "Human brains have
many more neurons than the Aplysia's, but it doesn't look
like there is any difference on a molecular or synaptic
"When this animal learns," Glanzman
said, "many changes take place in its nervous system.
I want to understand what causes these changes for certain
forms of learning; I want to understand everything there
is to understand. This knowledge will inform us about
the kinds of changes that take place in our brains when
Glanzman's quest for this knowledge will
be helped by his selection in November as one of eight
scientists awarded the prestigious Senator Jacob Javits
Award in the Neurosciences, which provides up to seven
years of research funding from the National Institute
of Neurological Disorders and Stroke (NINDS). The Jacob
Javits Award is presented to investigators who have "demonstrated
exceptional scientific excellence and productivity in
research areas supported by the NINDS and who are expected
to conduct cutting-edge research over the next seven years."
Glanzman's research may lead to such human
applications as developing interventions for people with
memory-related disorders and reducing age-related memory
Glanzman, who has been conducting research
on the marine snail for 20 years, said, "As far as
I can tell, everything that my colleagues and I have found
in the Aplysia has turned out to be relevant to nervous
systems in mammals. The original goal of Eric Kandel,
who founded this field and who won the 2000 Nobel Prize,
was to use the marine snail to understand human learning.
I expect there to be valuable lessons from the Aplysia
for age-related memory loss in humans."
The marine snail, which is substantially
larger than its garden-variety counterpart, has approximately
20,000 neurons in its central nervous system; humans have
approximately one trillion. Glanzman has a good understanding
of the functions of approximately 1,000 of the neurons.
The marine snail is native to California, living in tidal
waters off the coast.
With funding from the Jacob Javits Award,
Glanzman's laboratory will study topics including the
role of protein synthesis in long-term memory. In both
the Aplysia and mammals, learning that is spaced over
several hours induces long-term memory and turns on specific
genes in neurons, causing proteins to be synthesized that
have important functions in long-term memory. Glanzman's
team is identifying important genes and proteins, and
their functions in learning and memory.
What does the marine snail learn?
"The marine snail has to process information
about its environment, and it has to make associations
between different stimuli, just as we do," Glanzman
said. "It is capable of learning when an environment
is safe and when it is not, and of understanding the danger
posed by a predator."
Glanzman, whose appointments are in both
the UCLA College and UCLA's David Geffen School of Medicine,
is especially interested in the role of protein synthesis
in long-term memory.
"Long-term memory involves gene transcription
and protein synthesis," he said. "Our laboratory
has evidence that for long-term memory, protein synthesis
may occur at an earlier stage in memory formation than
was thought before. Then the questions are: What proteins
are being synthesized, where are they being synthesized
and what are they doing once they're synthesized? We will
use the Jacob Javitz Award to try to answer these questions."
One answer to what is synthesized may be
critically important receptors called AMPA glutamate receptors,
which mediate most synaptic transmission in the brain.
Glanzman is studying the role of AMPA receptors in learning.
In addition, Glanzman plans to start studying
a vertebrate: the zebra fish. It has many more neurons
than the marine snail, including some that are large and
mediate rapid reflexes.
"If you try to pick up a goldfish,
it seems to swim away from you quickly," Glanzman
said. "What really happens is the fish has an extremely
rapid escape response - a reflex that causes the fish
to bend its body in a 'C' shape, and then pushes it away
from you, and then the fish swims away. That startle reflex
is the first response, and that startle reflex is mediated
by large neurons known as Mauthner neurons. There is evidence
that the zebra fish possesses primitive forms of learning,
and more sophisticated forms of learning that the marine
snail does not show."
As a Stanford graduate student, Glanzman
began studying cognitive psychology and psycholinguistics,
but "kept getting more and more reductionistic in
my thinking. I wanted to understand how the brain actually
works. In the Aplysia, one understands what the physiological
and behavioral functions of individual neurons are. You
can look at a neuron in the Aplysia and say, 'That's a
motor neuron,' 'That's a sensory neuron.' We know that
the activity of those neurons has a significant role in
behavior. When looking at a change in a synaptic connection
between a pair of neurons in the Aplysia nervous system,
we know, for some of the neurons, what effect that will
have on behavior."
In earlier research, Glanzman's team identified
a cellular mechanism in the Aplysia that plays an important
role in learning and memory. A protein called the NMDA
receptor enhances the strength of synaptic connections
in the nervous system, and plays a vital role in memory
and in certain kinds of learning in the mammalian brain
as well. Glanzman's team demonstrated, in research published
in 1994, that strengthening of synaptic connections due
to activation of NMDA receptors (N-methyl D-aspartate)
is critical for learning in the marine snail.
Glanzman's research is funded by the National
Institute of Mental Health and the National Institute
of Neurological Disorders and Stroke. Reacting to his
selection for a Jacob Javits Award in the Neurosciences,
he said, "I'm very honored."
Higher invertebrates learn in complex ways,
said Glanzman, who noted that bees learn to associate
colors with nectar, and marine snails learn to identify
food, and to flee from predators.
"Our work implies that the brain mechanisms
for forming these kinds of associations might be extremely
similar in snails and higher organisms. People may think
invertebrates are not very sophisticated, but we don't
appreciate just how complicated their nervous systems
are, and how complex their behaviors are. We don't fully
understand even very simple kinds of learning in these
Original source: http://newsroom.ucla.edu/page.asp