Neural circuits for triggering saccades in the brainstem

Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Progress in brain research (Impact Factor: 5.1). 02/2008; 171:79-85. DOI: 10.1016/S0079-6123(08)00611-0
Source: PubMed

ABSTRACT Here we review the functional anatomy of brainstem circuits important for triggering saccades. Whereas the rostral part of the superior colliculus (SC) is considered to be involved in visual fixation, the caudal part of the SC plays an important role in generation of saccades. We determined the neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and omnipause neurons (OPNs) in the nucleus raphe interpositus. To reveal the neural mechanisms of triggering saccadic eye movements, we analysed the effects of stimulation of the SC on intracellular potentials recorded from IBNs and OPNs in anaesthetized cats. Our studies show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC, via contralateral IBNs. Further, IBNs receive disynaptic inhibition from the rostral part of the SC, on either side, via OPNs. Intracellular recording revealed that OPNs receive excitation from the rostral parts of the bilateral SCs, and disynaptic inhibition from the caudal SC mainly via IBNs. The neural connections determined in this study are consistent with the notion that the "fixation zone" is localized in the rostral SC, and suggest that IBNs, which receive monosynaptic excitation from the caudal "saccade zone," may inhibit tonic activity of OPNs and thereby trigger saccades.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectum's saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC-cMRF-RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2013; 33(41):16285-16296. DOI:10.1523/JNEUROSCI.2726-11.2013 · 6.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the past 15 years we have watched the unfolding of an enormous volume of information regarding HPV infections. Elaboration of the incredible genetic diversity of these viruses has been important to the development of laboratory tools for epidemiological investigations and will facilitate the future direction of studies targeting specific molecular mechanisms of disease. Through the use of these laboratory tools, HPV has been determined to be a necessary but not sufficient etiologic agent in the development of cervical cancer and other cancers of the anogenital tract. The duration of incident genital HPV infections has been partially established and this information demonstrates that most detectable HPV infections are transient. Recent observations of a second peak of cervical HPV prevalence in older women suggests the possibility that at least in some women, HPV infections may lay dormant at undetectable levels and subsequently become reactivated. The potential that older women may experience a reactivation of latent HPV infections, which may be accompanied by disease, requires further investigation. Current dogma concerning the long-term natural history of HPV infections awaits clarification by future studies. Furthermore, these future investigations remain important to appropriately characterize molecular processes within the host cell that are critical to the study of specific host immune responses to these infections.Research-grade PCR-based HPV tests continue to be important to ongoing and future epidemiological investigations that will better define HPV incidence at various anatomic sites. Of particular interest will be the elaboration of HPV infections at extragenital sites. In this regard, the potential contribution of HPVs to skin cancer outcomes is likely to become an intensive area of study. The use of HPV assays such as HC2 in large randomized clinical trials has established HPV testing as a viable option in the management of ASCUS Pap smears. Further clinical applications of various types of HPV testing, including applications to routine screening, remain an area of intensive research. In this regard, studies that examine quantities or levels of HPV genomes and specific HPV messages are currently underway. Probably the most exciting clinically relevant development of the past decade has been the implementation of clinical trials for HPV prophylactic vaccines. To date these trials have targeted cervical HPV infections. If prophylactic HPV vaccines can prevent incident HPV infection and CIN, maintenance of long-term vaccine immunity will need to be evaluated and establishment of any potential impact on the incidence of HPV-associated invasive cancers will be determined in one or two decades following widespread implementation.Many individuals and research groups have participated in contributing to understanding the epidemiology of HPV infections. As with the past two decades, future investigations concerning HPV infections will remain an area rich in discovery for all.
    Perspectives in Medical Virology 01/2002; DOI:10.1016/S0168-7069(02)08014-X
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intelligent agents balance speed of responding with accuracy of deciding. Stochastic accumulator models commonly explain this speed-accuracy tradeoff by strategic adjustment of response threshold. Several laboratories identify specific neurons in prefrontal and parietal cortex with this accumulation process, yet no neurophysiological correlates of speed-accuracy tradeoff have been described. We trained macaque monkeys to trade speed for accuracy on cue during visual search and recorded the activity of neurons in the frontal eye field. Unpredicted by any model, we discovered that speed-accuracy tradeoff is accomplished through several distinct adjustments. Visually responsive neurons modulated baseline firing rate, sensory gain, and the duration of perceptual processing. Movement neurons triggered responses with activity modulated in a direction opposite of model predictions. Thus, current stochastic accumulator models provide an incomplete description of the neural processes accomplishing speed-accuracy tradeoffs. The diversity of neural mechanisms was reconciled with the accumulator framework through an integrated accumulator model constrained by requirements of the motor system.
    Neuron 11/2012; 76(3):616-28. DOI:10.1016/j.neuron.2012.08.030 · 15.98 Impact Factor