Among the brain’s many specialized cells are Vasoactive Intestinal Peptide neurons, or VIP neurons. Their name comes from a peptide they produce, a small protein originally discovered for its effects on blood vessels in the digestive system. In the brain, however, this peptide and the neurons that release it have an influential role in managing the flow of information. These neurons are not the primary messengers that carry sensory information or motor commands, but act as regulators of local brain circuits, shaping how networks of other neurons behave.
Classification and Location of VIP Neurons
VIP neurons belong to a class of brain cells known as GABAergic interneurons. Interneurons are connectors that form circuits between other neurons rather than sending long-distance signals out of a brain region. The “GABAergic” designation means they use gamma-aminobutyric acid (GABA) as their primary neurotransmitter. GABA is the main inhibitory signal in the adult brain, reducing the activity of the neurons it targets and acting as a brake on neural circuits.
While found throughout the nervous system, VIP neurons are most concentrated in the cerebral cortex and the hippocampus. The cortex, the brain’s outer layer, is responsible for higher-order functions like thought, language, and consciousness. The hippocampus is located deep within the temporal lobe and is involved in learning and the formation of new memories.
Within the cortex, VIP neurons are most abundant in the superficial layers, closer to the surface of the brain. Their presence in these locations places them in a position to influence the complex computations underlying cognition and memory.
The Disinhibitory Function in Neural Circuits
Although VIP neurons release an inhibitory neurotransmitter, their signature function is one of “disinhibition.” This process is a double-negative form of control; instead of directly silencing active neurons, VIP neurons silence other inhibitory neurons. This action releases the brakes on a circuit, leading to an overall increase in activity.
The primary targets of VIP neurons are other types of GABAergic interneurons, most notably those that express somatostatin (SST). SST interneurons inhibit the brain’s principal excitatory neurons, which are the main carriers of information. When a VIP neuron becomes active, it releases GABA onto an SST interneuron, suppressing its activity. This stops the SST interneuron from inhibiting the principal neurons, allowing them to fire more freely.
An effective way to visualize this is to imagine a team of workers (the principal neurons) monitored by a guard (the SST interneuron). The guard’s presence prevents the workers from doing their job. The VIP neuron acts like a supervisor who instructs the guard to take a break. With the guard temporarily silenced, the workers are free to become active.
This disinhibitory circuit motif is a common strategy the brain uses to gate information and amplify specific signals when needed. This indirect method of excitation provides a way to selectively boost the signals of certain neuronal populations without a widespread increase in excitation, which could otherwise lead to instability.
Role in Regulating Behavior and Brain States
The disinhibitory mechanism of VIP neurons has far-reaching consequences for brain function and behavior. By selectively releasing the brakes on principal neurons, these cells help the brain adapt its processing to meet different demands. One prominent example is in sensory processing. In the visual cortex, VIP neurons help the brain filter and prioritize incoming information. This enhances the brain’s representation of an attended stimulus, effectively turning up the volume on what is important while tuning out distractions.
VIP neurons are also integral to regulating the body’s internal clock. A specific cluster of these neurons is found in the suprachiasmatic nucleus (SCN) of the hypothalamus, which acts as the brain’s master pacemaker for circadian rhythms. The coordinated activity of VIP neurons within the SCN is important for synchronizing daily cycles with the 24-hour light-dark cycle, including:
- Sleep
- Wakefulness
- Hormone release
- Metabolism
Their role also extends to learning and memory. The ability of the brain to change and adapt, known as synaptic plasticity, is the cellular basis of learning. In the hippocampus and cortex, VIP neuron-mediated disinhibition can facilitate the strengthening of connections between neurons, a process required for memory formation.
Implications in Neurological and Psychiatric Conditions
Dysfunction in VIP neurons is implicated in several neurological and psychiatric disorders. An imbalance in their activity can disrupt the equilibrium between excitation and inhibition in the brain, leading to disorganized processing and abnormal brain states. Evidence suggests a link between VIP neuron abnormalities and schizophrenia, a condition characterized by disordered thinking and perception. A failure in their disinhibitory control could contribute to the cognitive fragmentation seen in the disorder.
Because VIP neurons are involved in sensory processing, their dysfunction has been connected to autism spectrum disorders (ASD), where individuals often experience differences in sensory sensitivity. Changes in VIP signaling are also associated with epilepsy, a disorder defined by recurrent seizures. Since VIP neurons help regulate the excitability of principal cells, a reduction in their disinhibitory function could lower the seizure threshold and contribute to epileptogenesis.