How does the brain rapidly adjust the way it processes information as we shift between activities, levels of attention, and behavioral states? A new study suggests that the answer lies not simply in changes in the activity of individual neurons, but in how chemical signals reorganize the relationships among the properties that govern neuronal function.
Published in the Proceedings of the National Academy of Sciences (PNAS), the study, “Neuromodulatory control of cortical function: Cell-type-specific regulation of neuronal information transfer,” reveals that dopamine and acetylcholine, two chemical messengers essential for learning, attention, and cognitive flexibility, can fundamentally alter how neurons encode and transmit information.
The international research team, led by Tansu Celikel of Georgia Tech's School of Psychological and Brain Sciences and Fleur Zeldenrust of Radboud University in the Netherlands, found that these chemical signals influence different types of neurons in distinct ways. Their effects extend beyond changes in individual neuronal responses to reshape how multiple functional properties are organized and interact.
Beyond Turning Neurons Up or Down
Neurons process incoming information and communicate through electrical impulses known as action potentials. For decades, scientists have investigated how neuromodulators such as dopamine and acetylcholine influence this process, often focusing on whether these chemicals increase or decrease neuronal activity.
“Changes in neuronal activity alone do not necessarily tell us how effectively neurons process information,” explains Dr. Celikel. “A neuron that fires more frequently is not necessarily transmitting more useful information about its inputs. Likewise, a neuron that becomes less active may still play an important role in shaping how information is represented in the brain.”
The new study moves beyond conventional measures of neuronal activity by examining how neuromodulators affect multiple interacting properties, including the electrical characteristics of neuronal membranes, the generation of action potentials, adaptation to sustained stimulation, and sensitivity to incoming signals.
“Rather than acting like simple volume controls that turn neuronal activity up or down, dopamine and acetylcholine function as reconfiguration signals,” says Dr. Celikel. “They change not only how individual neurons respond, but also how the different components of neuronal information processing work together.”
Different Neurons, Different Responses
To investigate these effects, the researchers analyzed electrical recordings from excitatory and inhibitory neurons in the somatosensory cortex of mice, a brain region involved in processing sensory information, including touch.
Excitatory neurons generally promote activity within neural circuits, while inhibitory neurons help regulate and constrain that activity. The balance between these two populations is essential for normal brain function.
The researchers examined how activating three specific receptors, dopamine D1 and D2 receptors and the acetylcholine-sensitive muscarinic M1 receptor, influenced how neurons encode and transmit information.
Their findings revealed striking differences between neuronal populations and receptor types.
“Activating D1 receptors increased the amount of stimulus information transmitted by inhibitory neurons, while activating M1 receptors significantly reduced information transfer in excitatory neurons,” explains Dr. Celikel. “D2 receptor activation produced more modest effects, some of which were comparable to normal experimental variability.”
These findings challenge the assumption that increasing neuronal excitability necessarily improves information processing.
“What matters is not simply how much a neuron fires, but how effectively its activity represents incoming information,” adds Dr. Celikel. “Our results suggest that neuromodulators can selectively redistribute information processing across different neuronal populations.”
A More Flexible View of Neuronal Identity
Another important finding challenges traditional assumptions about how neurons are classified according to their functional characteristics.
Scientists commonly group neurons into functional categories based on properties such as their electrical activity, membrane characteristics, and responses to stimulation. These classifications are often treated as relatively stable.
However, the researchers discovered that activating neuromodulatory receptors reorganized how neurons clustered according to these properties.
Neurons that were functionally similar under baseline conditions could become more distinct following receptor activation, while previously dissimilar neurons could develop more closely related functional profiles.
“Our findings suggest that a neuron's functional identity is not entirely fixed, but depends in part on the chemical environment in which it operates,” says Dr. Celikel. “Rather than belonging to rigid, discrete functional categories, neurons may occupy a more flexible continuum of functional states.”
The researchers also discovered that neuromodulation reorganized the relationships among neuronal properties in different ways depending on the cell type.
Across the recorded populations, inhibitory neurons generally showed greater statistical coordination among their functional characteristics following receptor activation. Excitatory neurons, by contrast, exhibited a more selective reorganization, including greater independence between their sensitivity to incoming signals and other intrinsic properties.
This distinction suggests that neuromodulatory signals can shape the functional organization of neuronal populations in fundamentally different ways.
Together, the findings point to an additional dimension of neuronal regulation: brain chemicals influence not only individual cellular properties, but also how those properties relate to one another, potentially expanding the range of computational states available to neural circuits.
Implications for Understanding Brain Function
Dopamine and acetylcholine play essential roles in attention, learning, memory, and behavioral flexibility. Disruptions in neuromodulatory signaling are also implicated in neurological and psychiatric conditions, including Parkinson's disease and schizophrenia.
Understanding how these chemical systems reorganize neuronal information processing may help researchers develop more comprehensive explanations of how the brain adapts to changing behavioral demands and how these processes may be altered in disease.
The findings also highlight the importance of studying neuronal function beyond conventional measurements such as firing rates or excitability. By examining how different neuronal properties interact, researchers can gain a more complete understanding of how chemical signaling influences the brain's computational capabilities.
The current study examined individual neurons in isolated mouse brain tissue rather than measuring cognition or behavior directly. Further research will be needed to determine how these cellular changes influence the activity of larger neural networks and behavior in living animals.
Nevertheless, the findings establish a framework for understanding neuromodulation as a dynamic process that reorganizes neuronal computation rather than simply increasing or decreasing activity.
By demonstrating that dopamine and acetylcholine can reshape information transfer, functional classifications, and the relationships among neuronal properties, the study provides new insight into the cellular mechanisms that may enable the brain to adapt its information processing to changing conditions.
Publication information
Article: “Neuromodulatory control of cortical function: Cell-type-specific regulation of neuronal information transfer”
Journal: Proceedings of the National Academy of Sciences (PNAS)
Publication date: October 19, 2026
Related Media
Credit-Stock-image--Pexels
