A cholinergic mechanism underlies persistent neural activity necessary for eye fixation
Introduction
The eye moves in the horizontal plane under the action of two antagonist extraocular muscles: the lateral and medial recti. The lateral rectus muscle is innervated by motoneurons located in the pontine abducens nucleus, while the medial rectus muscle is innervated by motoneurons located in the mesencephalic oculomotor complex (Büttner-Ennever and Horn, 1997). As illustrated in Fig. 1, Fig. 2, these extraocular motoneurons are capable of evoking phasic firing (i.e., high-frequency bursts of action potentials lasting ≈100 ms) that will produce a strong muscular contraction which is able to generate a fast eye displacement — that is, a saccade or a fast phase of the vestibulo-ocular or opto-kinetic reflexes (Robinson, 1981; Moschovakis et al., 1996; Delgado-García, 2000). This fast muscular activation is necessary to overcome the viscous drag of the orbit. In order to maintain a stable position of the eye in the orbit, extraocular motoneurons are also capable of a sustained tonic firing, necessary to counteract the restoring elastic components of orbital tissues (Robinson, 1981; Escudero et al., 1992; Fukushima et al., 1992; Moschovakis, 1997; Delgado-García, 2000; Major and Tank, 2004). Thus, horizontal motoneurons encode the necessary velocity and position signals to rotate the eye toward the appropriate visual target and to hold the eye stable in the orbit. In fact, the firing properties of ocular motoneurons can be precisely represented by a first-order linear model (Robinson, 1981). In cats, horizontal motoneurons increase their mean firing rate by ≈7 spikes/s per degree of eye position, and by 1 spike/s per degree/s of eye velocity in the pulling direction of the involved muscle (see references in Delgado-García, 2000).
In the next few pages we will concentrate on experiments carried out by our group regarding the firing activities of prepositus hypoglossi (PH) neurons during eye movements, and on recent in vitro studies on the functional properties of reticular afferents to these neurons. More-detailed and comparative reviews regarding the integrative properties of PH neurons for the generation of eye-position signals can be found elsewhere (Robinson, 1981; Cannon and Robinson, 1987; Fukushima et al., 1992; Moschovakis et al., 1996; Moschovakis, 1997; Delgado-García, 2000; Major and Tank, 2004).
Section snippets
The final common pathway for horizontal eye movements
Abducens and medial rectus motoneurons represent the final common neural pathway interposed between eye-movement-related brainstem centers and extraocular muscles in the horizontal plane. Thus, abducens and medial rectus motoneurons must be able to translate to the lateral and medial recti muscles the precise neural motor commands corresponding to each type of eye movement (Robinson, 1981; Escudero and Delgado-García, 1988; Fukushima et al., 1992; Büttner-Ennever and Horn, 1997; Moschovakis,
Firing properties of prepositus hypoglossi neurons
Neurons located in the paramedian pontine reticular formation (PPRF), in particular those called excitatory burst neurons (EBN; Fig. 2), are able to generate bursts of action potentials that encode the amplitude, peak velocity, and duration of eye saccades and fast phases of the vestibulo-ocular and opto-kinetic reflexes (Igusa et al., 1980; Escudero and Delgado-García, 1988; Fukushima et al., 1992; Moschovakis et al., 1996). These neurons project monosynaptically onto abducens motoneurons and
The cascade model for the generation of eye-position signals
Using available data collected from extracellular recordings of firing activities of PH neurons during eye movements in alert cats, Delgado-García et al. (1989) have proposed a neural circuit in cascade to explain the generation of eye-position signals. In this circuit, the three neuronal types described above (velocity-position, position-velocity, and position neurons) were assumed to receive similar inputs from vestibular and reticular origins. This early proposal was modified following data
In search of a synaptic mechanism for eye fixation
As shown by Aksay et al. (2001), the sustained firing rate observed in the neural integrator subserving eye position does not depend on neuronal intrinsic properties, but has to be ascribed to the amplitude and rate of the synaptic inputs arriving at the integrator (brainstem area I, where position-related neurons are located in goldfish). It has also been proposed that synaptic feedback among neurons located in the brainstem area I is still necessary for temporal integration (Aksay et al., 2003
The cholinergic connection
The diagrams illustrated in Fig. 8, Fig. 9, Fig. 10 attempt to summarize the results obtained by our group in a recent series of in vitro and in vivo experiments (Navarro-López et al., 2004, Navarro-Lopez et al., 2005).
The electrical stimulation of the PPRF (i.e., of EBN; Fig. 8) by single pulses evokes a monosynaptic depolarization of PH neurons (Igusa et al., 1980). The PPRF synapse is glutamatergic in nature, acting on AMPA/kainate receptors. It has been shown (Navarro-López et al., 2004)
Abbreviations
- AMPA
alpha-amino-3-hydroxy-5-methylisoxazole propionate
- NMDA
N-methyl-d-aspartate
- PH
prepositus hypoglossi
- PPRF
paramedian pontine reticular formation
Acknowledgments
We acknowledge the editorial help of Mr. R. Churchill. The authors thank the help of Dr. Agnès Gruart in the edition of the figures. This work was supported by grant BFI2000-00939 from the Spanish Ministry of Science.
References (43)
- et al.
Anatomical substrates of oculomotor control
Curr. Opin. Neurobiol.
(1997) Why move the eyes if we can move the head?
Brain Res. Bull.
(2000)- et al.
Behavior of neurons in the abducens nucleus of the alert cat. II. Internuclear neurons
Neuroscience
(1986) - et al.
A neurophysiological study of PH neurons projecting to oculomotor and preoculomotor nuclei in the alert cat
Neuroscience
(1989) - et al.
The neuronal substrate of integration in the oculomotor system
Prog. Neurobiol.
(1992) Network memory
Trends Neurosci.
(1997)Cellular basis of working memory
Neuron
(1995)Burst as a unit of neuronal information: making unreliable synapses reliable
Trends Neurosci.
(1997)- et al.
Persistent neural activity: prevalence and mechanisms
Curr. Opin. Neurobiol.
(2004) - et al.
Nitric oxide production by brainstem neurons is required for normal performance of eye movements in alert animals
Neuron
(1996)
The microscopic anatomy and physiology of the mammalian saccadic system
Prog. Neurobiol.
Single cholinergic mesopontine tegmental neurons project to both the pontine reticular formation and the thalamus in the rat
Neuroscience
Correlated discharge among cell pairs within the oculomotor horizontal velocity-to-position integrator
J. Neurosci.
In vivo intracellular recording and perturbation of persistent activity in a neural integrator
Nat. Neurosci.
Synthesis of horizontal conjugate eye movement signals in the abducens nucleus
Jap. J. EEG EMG Suppl.
Loss of the neural integrator of the oculomotor system from brain stem lesions in monkey
J. Neurophysiol.
Integrator function in the oculomotor system is dependent on sensory context
J. Neurophysiol.
Disabling of the oculomotor neuronal integrator by kainic acid injections in the prepositus-vestibular complex of the cat
J. Physiol. (Lond.)
Behaviour of medial rectus motoneurons in the alert cat
Eur. J. Neurosci.
Graded persistent activity in entorhinal cortex neurons
Nature
Behavior of reticular, vestibular and prepositus neurons terminating in the abducens nucleus of the alert cat
Exp. Brain Res.
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