Garrett Neske, PhD, assistant professor of physiology and biophysics in the Jacobs School of Medicine and Biomedical Sciences, is studying fundamental communication between the cortex and thalamus with new funding from the Whitehall Foundation.
Exploring Neural Networks Behind Brain Communication
New Grant Focuses on How Acetylcholine, a Chemical Neuromodulator, Could Boost Brain Signaling in More Ways Than Previously Known
By Keith Gillogly
Published January 8, 2026
To study how a key chemical neuromodulator affects signaling in the brain's cortex, Garrett Neske, PhD, has received a three-year, $300,000 grant from the Whitehall Foundation, a nonprofit organization funding basic neurobiology research.
Neske is assistant professor of physiology and biophysics in the Jacobs School of Medicine and Biomedical Sciences. His investigations into neuromodulators and brain communication could enhance our fundamental understanding of perception and attention and of related neurodegenerative and neuropsychiatric diseases.
Cortex and Thalamus in Focus
Neske’s research broadly focuses on functional interactions between the brain’s cortex and thalamus. The cortex comprises the outermost layer of the brain while the thalamus lies deeper within. “Together the cortex and the thalamus are responsible for many of the higher-level features of perception, motor control, and cognition,” Neske says.
The brain’s normal functioning depends on fluid inter-cortex signaling and on the cortex and thalamus synchronizing communication. Doing so involves the thalamus receiving input from the cortex, processing that information via an intermediary structure known as the higher order thalamus, and then sending out new signals to various cortical regions.
These thalamocortical outputs flowing out of the higher order thalamus are a key, if understudied, communication route, Neske says. He and his colleagues are specifically looking at acetylcholine, a chemical neuromodulator released in the brain during instances of high attention and arousal.
To better understand how acetylcholine modulates information flow across thalamic and cortical circuits, Neske and his colleagues will study how the neuromodulator fine tunes cortical synapses, the junctions between neurons that relay chemical signals.
“Remarkably, we know very little about how acetylcholine is modulating these synapses outside of the very initial stages of central processing,” Neske says.
Investigating More Complex, Distant Cortical Regions
During initial sensory processing, acetylcholine has been observed to enhance thalamic input to the cortex by boosting release of excitatory neurotransmitters while suppressing intracortical synapses, Neske says. Parts of the cortex are essentially quieted down so that the brain can focus on the information coming from the thalamus.
But this acetylcholine-driven enhanced thalamic activity could extend beyond early-stage processing and involve more complex processing in distant cortical regions, Neske suggests. If so, it could alter our understanding of attention, memory formation, cognitive flexibility and other fundamental neurologic processes.
In these distant, more complex cortical regions, the researchers hypothesize that acetylcholine release will have a more significant effect on brain circuits that pass information through the thalamus compared to cortical circuits that communicate directly without involving the thalamus. They also believe that the axons, or nerve fibers, of the higher order thalamus possess the same acetylcholine-binding nicotinic receptors as those found on axons within thalamic circuits used in initial, early-stage communication.
Neuromodulators Involved with Many Brain Diseases
The researchers will work to simultaneously track acetylcholine release and communication between brain regions using both living mouse models and extracted brain slices.
“A major feature of my lab is to have these projects that have a slice and synaptic physiology component along with an in vivo component that looks at how these circuits are engaged in real life,” Neske says.
Mice implanted with optic fibers in their brains will be shown visual stimuli — in this case water to trigger thirst. Fluorescent signals will then be used to detect acetylcholine release and assess thalamic and cortical axon activity.
The researchers will also examine mouse brain slices using optogenetics, a technique to study neuronal activity using light-sensitive proteins. They will investigate how acetylcholine potentially enhances release of glutamate, an excitatory neurotransmitter, in the higher order thalamus.
Glutamate activates neuronal activity, driving learning, new connections, and information processing. So, boosted glutamate release could indicate that the thalamus plays an even larger role in dynamically processing and prioritizing information across more distant cortical regions.
While this basic science research focuses on exploratory investigation, the cholinergic system, which involves acetylcholine release, is involved in many brain diseases. “There are a wide range of different diseases where cholinergic signaling is impaired, from neurodegenerative diseases like Alzheimer’s disease to neuropsychiatric diseases like schizophrenia,” Neske says.
Neske further notes that acetylcholine is but one of the major neuromodulators affecting thalamocortical communication and brain circuitry, suggesting other avenues for future investigation.
“The big picture is to understand how the mechanisms by which these different neuromodulators affect synaptic signaling pathways throughout the cortex, not just within a cortical area but across cortical areas,” he says.
