1. Polysynaptic pathways from the vestibular nuclei to the lateral mamillary nucleus of the rat: substrates for vestibular input to head direction cells J. E. Brown, J. P. Card, B. J. Yates Exp Brain Res (2005) 161: 47-61 Presented by Lianne K. Morris-Smith NS&B275, 3/1/2005

2. Abstract The activity of some neurons in the lateral mammillary nucleus (LMN) of the rat corresponds with the animal’s current head direction (HD). HD cells have been studied extensively but the circuitry responsible for the generation and maintenance of the HD signal has not been established. The present study tested the hypothesis that a polysynaptic pathway connects the vestibular nuclei with the LMN via one or more relay nuclei. This circuitry could provide a substrate for the integration of sensory input necessary for HD cell activity. This hypothesis is based upon the prior demonstration that labyrinthectomy abolishes HD selectivity in thalamic neurons. Viral transneuronal tracing with pseudorabies virus (PRV) was used to test this hypothesis. We injected recombinants of PRV into the LMN and surrounding nuclei of adult male rats and defined the patterns of retrograde transneuronal infection at survival intervals of 60 and 72 h. Infected medial vestibular neurons (MVN) were only observed at the longest postinoculation interval in animals in which the injection site was localized largely to the LMN. Robust infection of the dorsal tegmental nucleus (DTN) and nucleus prepositus hypoglossi (PH) in these cases, but not in controls, at both survival intervals identified these nuclei as potential relays of vestibular input to the LMN. These data are consistent with the conclusion that vestibular information that contributes to the LMN HD cell activity is relayed to this caudal hypothalamic cell group via a polysynaptic brainstem circuit. (From: J. E. Brown, J. P. Card, B. J. Yates Exp. Brain Res (2005) 161: 47-61)

3. Hypothesis “A polysynaptic pathway connects the vestibular nuclei with the LMN via one or more relay nuclei.”

4. Areas that were of particular interest (and why) LMN: bilateral lesions of LMN lead to loss of directional specificity of ADN HD cells (Blair et al, 1999) Vestibular nuclei: abolishing labyrinthine input eliminates directional sensitivity of HD cells in ADN (Stackman and Taube, 1997) DTN: known to receive vestibular input; some DTN neurons code for angular head velocity; small percentage of DTN are “classic” HD cells SUG and PH: receive vestibular input; project to DTN; thought to be involved in oculomotor pathways

5. Study used Pseudorabies Virus (PRV) PRV is taken up by axon terminals and transported retrogradely from injection site PRV can “jump” synapses Brown et al. used two different recombinants of PRV: PRV BaBlu (expresses β-gal) and PRV-152 (expresses enhanced GFP)

6. Photomicrographs of an injection site (a) and retrogradely infected brainstem nuclei (b-d), 60-hour survival time animal

7. Photomicrographs of an injection site (a) and retrogradely infected brainstem nuclei (b-f), 72-hour survival time animal

8. Distribution of infected neurons from case shown in Fig. 2

9. Conclusion