Abolition of lemniscal barrellette patterning in Prrxl1 knockout mice: Effects upon ingestive behavior

Abstract

Ingestive behaviors in mice are dependent on orosensory cues transmitted via the trigeminal nerve, as confirmed by transection studies. However, these studies cannot differentiate between deficits caused by the loss of the lemniscal pathway vs. the parallel paralemniscal pathway. The paired-like homeodomain protein Prrxl1 is expressed widely in the brain and spinal cord, including the trigeminal system. A knockout of Prrxl1 abolishes somatotopic barrellette patterning in the lemniscal brainstem nucleus, but not in the parallel paralemniscal nucleus. Null animals are significantly smaller than littermates by postnatal day 5, but reach developmental landmarks at appropriate times, and survive to adulthood on liquid diet. A careful analysis of infant and adult ingestive behavior reveals subtle impairments in suckling, increases in time spent feeding and the duration of feeding bouts, feeding during inappropriate times of the day, and difficulties in the mechanics of feeding. During liquid diet feeding, null mice display abnormal behaviors including extensive use of the paws to move food into the mouth, submerging the snout in the diet, changes in licking, and also have difficulty consuming solid chow pellets. We suggest that our Prrxl1^−/− animal is a valuable model system for examining the genetic assembly and functional role of trigeminal lemniscal circuits in the normal control of eating in mammals and for understanding feeding abnormalities in humans resulting from the abnormal development of these circuits.

• Barrellettes
• ingestive behavior
• principal trigeminal nucleus

Acknowledgements

This research was partially supported by the NIH SC1 Grant SC1 GM088114-01A1 and by a CUNY Collaborative Incentive Research Grant (H. P. Zeigler and P. Feinstein). This publication was made possible by a Research Centers in Minority Institutions Program grant from the National Institute on Minority Health and Health Disparities (MD007599) of the National Institutes of Health. The authors wish to thank Asaf Keller for technical assistance and training in histological techniques, Alex Keene for comments that greatly improved the manuscript, Zachary Jones for camera training and laboratory assistance, and Thomas Preuss for help and advice.

Declaration of interest

The authors report no conflicts of interest.