Harvard University. US: Like musical sounds, different states of mind are defined by
distinct, characteristic waveforms, recognizable frequencies and rhythms
in the electrical field of the brain. When the brain is alert and
performing complex computations, the cerebral cortex, the wrinkled outer
surface of the brain, thrums with cortical band oscillations in the
gamma wavelength; in some neurological disorders like schizophrenia,
these waves are out of tune and the rhythm is out of sync.
New research led by Harvard Medical School researchers at the VA
Boston Healthcare System (VABHS) has identified a specific class of
neurons—basal forebrain GABA parvalbumin neurons, or PV neurons—that
trigger these waves, acting as neurological conductors that trigger the
cortex to hum rhythmically and in tune.
The results appear this week in PNAS.
“This is a move toward a unified theory of consciousness control,” said co-senior author Robert McCarley,
HMS professor of psychiatry and head of the Department of Psychiatry at
VA Boston Healthcare System. “We’ve known that the basal forebrain is
important in turning consciousness on and off in sleep and wake, but now
we’ve found that these specific cells also play a key role in
triggering the synchronized rhythms that characterize conscious thought,
perception and problem solving.”
McCarley added that understanding the mechanism the brain uses to
sync up for coherent, conscious thought may suggest potential therapies
for disorders like schizophrenia, where the brain fails to form these
characteristic waves.
“Our brains need a coherence of firing to organize perception and
analysis of data from the world around us,” McCarley said. “What we
found is that the PV neurons in the basal forebrain fine tune cognition
by putting into motion the oscillations required for higher thinking.”
When they began their investigation, the researchers suspected that
the subcortical PV neurons might play a role in regulating cortical
gamma band oscillations because they are found in the basal forebrain,
an area of the brain that is responsible for switching the brain between
waking and sleeping states. While many researchers believed that the
cholinergic neurons—another class of neurons located nearby—were the key
to the process, McCarley’s team thought that the PV neurons seemed like
more likely candidates because they physically reach out toward PV GABA
neurons in the cortex.
To test this theory, the researchers needed to be able to selectively
activate different types of neurons. Using a technique called
optogenetics, where cells are genetically altered with photosensitive
switches, the researchers toggled the PV neurons on and off using laser
light.
When the PV neurons were switched on, the cortex of the animals
showed more of the gamma activity typical of conscious states. Other
experiments were performed to rule out the nearby cholinergic neurons,
and to test neuronal firing in vitro. The results showed that PV neurons
are necessary to initiate cortical band oscillations, and that they did
not rely on other neurons to help trigger synchronized oscillations.
The cortex, where higher-level thinking takes place, is the home of
consciousness. If the basal forebrain plays a role in switching the
cortex between waking and sleeping states, perhaps the PV neurons play a
role in more fine-grained aspects of consciousness.
The chemical that the PV neurons use to transmit their signal, GABA,
is a neural inhibitor. When the PV cells fire, they inhibit the PV
receptor neurons in the cortex, switching them all off at the same time.
A beat later, the neurons in the cortex then switch back on, firing all
at once. Repeated again and again, this process creates a synchronized,
pulsing rhythm, with all of the neurons firing in coordination like
musicians playing the same notes in a round over and over again.
McCarley, who has spent much of his clinical career working with
patients with schizophrenia, said it was particularly gratifying to be
able to bring together his research and his clinical interests, and
noted that the study was the result of cross-disciplinary work by a team
with expertise in brain anatomy, mathematics, wave theory and both in
vivo and in vitro neurophysiology. Collaborators included co-first
authors Tae Kim and Stephen Thankachan, both HMS instructors in
psychiatry at the VABHS, and co-senior author Ritchie Brown, HMS Assistant Professor of Psychiatry at the VABHS.
This research was performed at the Brockton campus of the VABHS and
supported by Department of Veterans Affairs Merit Awards; by National
Institute of Mental Health Grants R01 MH039683, R21 MH094803 and R01
MH100820; the National Institute of Neurological Disorders and Stroke
Grants R21 NS079866-01; the National Heart Lung and Blood Institute
Grant P01 HL095491; and the Global Frontier Grant 2011-0031525.
Article #14-13625: “Cortically projecting basal forebrain parvalbumin
neurons regulate cortical gamma band oscillations,” by Tae Kim et al. Proceedings of the National Academy of Sciences.