Afferent Projections to the Calca/CGRP-Expressing Parabrachial Neurons in Mice

Area of Science:

• Neuroscience
• Neuroanatomy
• Sensory Processing

Background:

• The parabrachial nucleus (PB) in the dorsolateral pons processes interoceptive and cutaneous sensory signals.
• A subpopulation of lateral PB neurons expresses the Calca gene, coding for calcitonin gene-related peptide (CGRP).
• These PB^Calca/CGRP neurons are involved in threat responses (hypercarbia, pain, nausea) but their inputs are not fully understood.

Purpose of the Study:

• To comprehensively map the afferent projections to the lateral PB.
• To specifically identify monosynaptic inputs targeting PB^Calca/CGRP neurons.
• To elucidate the neurochemical identity of these inputs and their functional connections.

Main Methods:

• Conventional cholera toxin B subunit (CTb) retrograde tracing.
• Conditional rabies virus retrograde tracing for monosynaptic input mapping.
• Vesicular GABA (vGAT) and glutamate (vGLUT2) transporter reporter mice.
• Anterograde tracing and confocal microscopy.
• Channelrhodopsin-assisted circuit mapping.

Main Results:

• Lateral PB neurons receive GABAergic inputs from the amygdala, bed nucleus of the stria terminalis, substantia innominata, and periaqueductal gray.
• Glutamatergic inputs originate from the cortex, paraventricular nucleus, parasubthalamic nucleus, trigeminal complex, medullary reticular nucleus, and nucleus of the solitary tract.
• GABAergic neurons in the central amygdala directly inhibit PB^Calca/CGRP neurons.

Conclusions:

• Established a detailed neuroanatomical framework for afferent connections to lateral PB.
• Identified specific inhibitory and excitatory inputs regulating PB^Calca/CGRP neuron activity.
• Provided insights into the neural circuitry underlying threat detection and response.