Q&A Report: Sensorimotor Network Development During Early Postnatal Life in the Awake and Sleeping Brain

J. Dooley: The biggest advantage of the Mobile HomeCage for us was the pup’s ability to locomote while remaining headfixed. Because we do acute experiments, and because we found that rat pups quickly habituate to these recording conditions so long as they can locomote freely, this was the ideal experimental setup for us.

A. Cavaccini: The mobile home cage allows us to perform electrophysiological recordings on head-fixed neonatal mice that can locomote. Due to the weight and size of current implants we cannot perform such recordings on freely moving neonatal mice.

J. Dooley: Although not quantitative per-se, because my research is interested in neural activity during sleep, and infant rats do not readily sleep if they are stressed, we are confident that within an hour after being head-fixed (when pups begin cycling between sleep and wake) they have habituated to the Mobile HomeCage. In addition to cycling between sleep and wake, it’s worth mentioning that after about 15 minutes in the Mobile HomeCage, the pups do not vocalize or exhibit any other signs of distress (e.g., struggling against head-fix).

J. Dooley: All of the recording sites (and pharmacological manipulations) were confirmed histologically – but this was left out of the talk for time constraints. However, for what it’s worth, the coordinates for VL and VP were quite similar between 12 and 20 days of age. The biggest change was in the anterior-posterior axis, with the center of VL being ~2.1 mm caudal to bregma at 12 days of age, and ~2.3 mm caudal to bregma at 20 days of age. We found a similar difference in VP, which overall is caudal to VL.

A. Cavaccini: Yes, the recording coordinates for the striatum change depending on the age of the mouse or the rat (although we have not worked with the latter).

A. Cavaccini: I would say that they recover enough. I have observed that the average travel distance of mouse pups <P13 in my experiments is similar to the one recorded by van der Bourg A. and colleagues (Cerebral Cortex, 2017) in freely moving mouse pups of the same age.

A. Cavaccini: My experiments last one single day. In order to do a longitudinal electrophysiological experiment for many days I would need to prepare a chronic implant on a mouse pup, which is unfortunately not as straight forward.

J. Dooley: As mentioned above, we found that generally within 1 hour, and almost certainly within 2 hours, pups had habituated to the Mobile HomeCage, cycling between sleep (including both slow-wave sleep and REM sleep) and wake. Behaviors during wake include locomotion and grooming.

J. Dooley: Even in non-clinical conditions, twitching is rarely the topic of scientific inquiry, and in clinical conditions, even less so. Greta Sokoloff, another member of the Blumberg Lab, has recently begin investigating twitching in human infants, including potentially investigating whether differences in twitching can provide diagnostic insights into sensorimotor disorders, but it’s still early days for this work. Stay tuned!

A. Cavaccini: In a J. Physiology paper of 2019 Krajeski R.N. and colleagues have shown through electrophysiological recordings in ex-vivo acute brain slices, that in the first postnatal week both excitatory and inhibitory synapses are already functional on striatal projection neurons (SPNs). However, there are some changes implying a first crosstalk between SPNs, through gap junctions, which in the second and later postnatal weeks leave the stage to inhibitory synaptic connections. Considering that, I would say that inhibition is already there at P11, but what exactly takes place over the course of development is still unclear.

J. Dooley: Yes, we certainly can record from VL and the DCN simultaneously. We’ve just started to record from cerebellar structures at these ages, so hopefully the lab will have something to report.  Stay tuned!

A. Cavaccini: Yes, being in a different environment may increase locomotion in a P10 mouse pup.