Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks.

Area of Science:

• Neuroscience
• Molecular Biology
• Systems Neuroscience

Background:

• Single-cell transcriptomics classifies mammalian brain neurons.
• Systems neuroscience traditionally analyzes neuronal encoding without cell-type specificity.
• Understanding cell-type specific neuronal function is crucial for brain research.

Purpose of the Study:

• To investigate the relationship between transcriptomic cell types of mouse prefrontal cortex (PFC) projection neurons, their axonal projections, and their encoding properties across cognitive tasks.
• To determine if molecularly defined neuron types exhibit distinct functional roles in behavior.

Main Methods:

• Utilized single-cell transcriptomics to classify PFC projection neuron types.
• Traced axonal projections of identified neuron types.
• Measured Ca2+ activity in specific neuron populations during two-alternative choice tasks in freely moving mice.
• Compared encoding properties of molecularly homogeneous PFC→periaqueductal gray (PAG) neurons with heterogeneous classes.

Main Results:

• Most PFC neuron types projected to multiple targets, and most targets received input from multiple types, with PFC→PAG being an exception.
• All examined cell types qualitatively contained task-related signals.
• PFC→PAG neurons most potently encoded choice in cued tasks.
• Contralateral PFC-projecting neurons most potently encoded reward context in an uncued task.

Conclusions:

• Neuronal task signals are organized redundantly across different cell types.
• Specific molecular-anatomical neuron types exhibit quantitative biases in encoding task-related information.
• This highlights the importance of integrating molecular and systems neuroscience approaches.