The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.
Animals ; Neurons/physiology* ; Mice ; Prefrontal Cortex/cytology* ; Parvalbumins/metabolism* ; Brain Mapping/methods* ; Neural Pathways/physiology* ; Somatostatin/metabolism* ; Male ; Interneurons/physiology* ; Mice, Inbred C57BL ; Thalamus/physiology* ; Mice, Transgenic

The pedunculopontine nucleus (PPN) is located in the dorso-lateral part of the ponto-mesencephalic tegmentum. The PPN is composed of two groups of neurons: one containing acetylcholine, and the other containing non-cholinergic neurotransmitters (GABA, glutamate). The PPN is connected reciprocally with the limbic system, the basal ganglia nuclei (globus pallidus, substantia nigra, subthalamic nucleus), and the brainstem reticular formation. The caudally directed corticolimbic-ventral striatal-ventral pallidal-PPN-pontomedullary reticular nuclei-spinal cord pathway seems to be involved in the initiation, acceleration, deceleration, and termination of locomotion. This pathway is under the control of the deep cerebellar and basal ganglia nuclei at the level of the PPN, particularly via potent inputs from the medial globus pallidus, substantia nigra pars reticulata and subthalamic nucleus. The PPN sends profuse ascending cholinergic efferent fibers to almost all the thalamic nuclei, to mediate phasic events in rapid-eye-movement sleep. Experimental evidence suggests that the PPN, along with other brain stem nuclei, is also involved in anti-nociception and startle reactions. In idiopathic Parkinson's disease (IPD) and parkinson plus syndrome, overactive pallidal and nigral inhibitory inputs to the PPN may cause sequential occurrences of PPN hypofunction, decreased excitatory PPN input to the substantia nigra, and aggravation of striatal dopamine deficiency. In addition, neuronal loss in the PPN itself may cause dopamine-r esistant parkinsonian deficits, including gait disorders, postural instability and sleep disturbances. In patients with IPD, such deficits may improve after posteroventral pallidotomy, but not after thalamotomy. One of the possible explanations for such differences is that dopamine-resistant parkinsonian deficits are mediated to the PPN by the descending pallido-PPN inhibitory fibers, which leave the pallido-thalamic pathways before they reach the thalamic targets.
Animal ; Basal Ganglia/cytology ; Human ; Mesencephalon/physiology* ; Mesencephalon/cytology ; Movement Disorders/etiology* ; Pons/physiology* ; Pons/cytology ; Thalamus/cytology