The Periaqueductal Gray Orchestrates Sensory and Motor Circuits at Multiple Levels of the Neuraxis.
The periaqueductal gray (PAG) coordinates behaviors essential to survival, including striking changes in movement and posture (e.g., escape behaviors in response to noxious stimuli vs freezing in response to fear-evoking stimuli). However, the neural circuits underlying the expression of these behaviors remain poorly understood. We demonstrate in vivo in rats that activation of the ventrolateral PAG (vlPAG) affects motor systems at multiple levels of the neuraxis through the following: (1) differential control of spinal neurons that forward sensory information to the cerebellum via spino-olivo-cerebellar pathways (nociceptive signals are reduced while proprioceptive signals are enhanced); (2) alterations in cerebellar nuclear output as revealed by changes in expression of Fos-like immunoreactivity; and (3) regulation of spinal reflex circuits, as shown by an increase in α-motoneuron excitability. The capacity to coordinate sensory and motor functions is demonstrated in awake, behaving rats, in which natural activation of the vlPAG in fear-conditioned animals reduced transmission in spino-olivo-cerebellar pathways during periods of freezing that were associated with increased muscle tone and thus motor outflow. The increase in spinal motor reflex excitability and reduction in transmission of ascending sensory signals via spino-olivo-cerebellar pathways occurred simultaneously. We suggest that the interactions revealed in the present study between the vlPAG and sensorimotor circuits could form the neural substrate for survival behaviors associated with vlPAG activation.


CONCLUSIONS
Neural circuits that coordinate survival behaviors remain poorly understood. We demonstrate in rats that the periaqueductal gray (PAG) affects motor systems at the following multiple levels of the neuraxis: (1) through altering transmission in spino-olivary pathways that forward sensory signals to the cerebellum, reducing and enhancing transmission of nociceptive and proprioceptive information, respectively; (2) by alterations in cerebellar output; and (3) through enhancement of spinal motor reflex pathways. The sensory and motor effects occurred at the same time and were present in both anesthetized animals and behavioral experiments in which fear conditioning naturally activated the PAG. The results provide insights into the neural circuits that enable an animal to be ready and able to react to danger, thus assisting in survival.
School of Physiology, Pharmacology, and Neuroscience, and School of Biological Sciences, University of Bristol, Bristol BS8 1TQ, United Kingdom.
Stella
S
Koutsikou
School of Physiology, Pharmacology, and Neuroscience, and Neuroscience Paris Seine, Cerebellum, Navigation and Memory Team, Sorbonne Universities, Université Pierre et Marie Curie, University of Paris 06 Unité Mixte de Recherche Scientifique 8246, INSERM Unité Mixte de Recherche Scientifique 1130, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 8246, F-75005 Paris, France.
Thomas C
TC
Watson
School of Physiology, Pharmacology, and Neuroscience, and.
Jonathan J
JJ
Crook
School of Physiology, Pharmacology, and Neuroscience, and.
J Lianne
JL
Leith
School of Physiology, Pharmacology, and Neuroscience, and.
Charlotte L
CL
Lawrenson
School of Physiology, Pharmacology, and Neuroscience, and R.Apps@bristol.ac.uk.
Richard
R
Apps
School of Physiology, Pharmacology, and Neuroscience, and.
Bridget M
http://orcid.org/0000-0002-0268-6419
BM
Lumb
D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D002531:Cerebellum / Q000502:physiology; D003213:Conditioning, Psychological; D004525:Efferent Pathways / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D019054:Evoked Potentials, Motor / Q000502:physiology; D005239:Fear; D006181:H-Reflex; D006614:Hindlimb / Q000502:physiology; D008297:Male; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000166:cytology / Q000502:physiology*; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014851:Wakefulness
D016761:Oncogene Proteins v-fos
cerebellum; fear; nociception; periaqueductal grey; proprioception; spinal cord