Vicente Montero

Professor (emeritus)
M.D., 1961, University of Chile

Contact Information
Email: vmontero@facstaff.wisc.edu
(608) 231-2630 Phone
(608) 231-3328 Fax

Research Interests
Neural basis of attention: Role of corticothalamic pathways and thalamic reticular nucleus in attention mechanisms

Although the brain of conscious animals and humans is constantly inundated by myriads of stimuli of different kinds (visual, acoustic, etc.), only a fraction reaches awareness and control of behavior. Selective attention filters relevant from behaviorally irrelevant stimuli. There is considerable evidence in monkeys and humans that responses in visual cortical areas, including the primary visual cortex, can be modulated by visual attention. However, the neural mechanisms underlying this modulation are not understood.

In a study⁸ that combined a behavioral paradigm in which normal rats are naturally paying attention to the environment (exploration of a novel-complex environment, NCE) and a marker of neuronal activity at single cell level (expression of the immediate-early gene c-fos)⁷, we found that in normal exploring rats there is preferential activation of the visual sector of the thalamic reticular nucleus (TRN), located caudodorsally in the nucleus. By contrast, in blind exploring rats there is instead preferential activation of the somatic sector in central TRN. In both types of animals there was absence of activation in the acoustic sector of TRN, located caudoventrally in the nucleus, despite attentional irrelevant noises generated by exploration which induced fos expression in brainstem acoustic centers. These results suggest that different sensory sectors of the TRN are activated in the alert animal depending on prevalent sensory cues used for recognition of the environment or that have behavioral significance, and that the TRN plays a crucial role in attention mechanisms at subcortical levels.

The TRN is a sheet of GABAergic inhibitory neurons⁴ placed laterally in the thalamus of mammals. It is strategically located to influence thalamocortical interactions by virtue of being in the pathway of thalamocortical and corticothalamic axons, from which it receives synapses⁵, and projecting back inhibitory synapses into the dorsal thalamus^2,3. The visual sector of TRN (TRNv) receives a robust, retinotopically organized projection from the primary visual cortex (V1)¹ suggesting a precise cortical control of this structure.

Research projects in my lab are focused on determining the neural basis of TRNv activation in the attentive animal, and the role that this activation plays in mechanisms of attention. A working ‘focal attention’ hypothesis postulates that the observed activation of TRNv in exploring animals is necessarily a reflection of activation of the corticogeniculate pathway originating in layer 6 of V1, because these axons innervate both the lateral geniculate nucleus (LGN) and the visual reticular segment. ‘Top down’ inputs from a focus of attention in V1 generates a core of excitation in LGN via direct glutamatergic corticogeniculate pathways⁶, and surround inhibition mediated by more dispersed cortico-reticulo-geniculate (ultimately GABAergic) pathways. In this way, thalamocortical transmission of a focus of attention is enhanced relative to diminished transmission of surrounding regions of the visual field.

Figure: Attention-dependent Fos-activation of the visual segment of the thalamic reticular nucleus (TRNv) in the rat induced by exploration of a novel-complex environment. In contrast, the acoustic segment of the nucleus (TRNa) is not activated, despite acoustic stimulation generated by exploration, but which is attention irrelevant. Coronal section.

Results consistent with this hypothesis have been obtained: a) In rats rendered monocular amblyopic by visual deprivation, there is a drastic decrease of attention-dependent neuronal activation in TRNv and in layer 6 of V1 contralateral to the amblyopic eye, in comparison to strong activation of these structures in the side contralateral to the normal eye⁹. Since amblyopia is known to be a cortical and not a geniculate abnormality, and there is diminished activation in layer 6 but not in LGN of these rats, the results suggest that attentional activation of TRNv is dependent on visual cortex inputs ‘top-down’ inputs from the primary visual cortex originating in layer 6. b) Direct evidence of dependence of attentional activation of TRNv on top-down inputs from V1 was obtained in rats with unilateral excitotoxic lesions restricted to layer 6 of V1 which explored the NCE. In these animals there was a highly significant diminution of neuronal activation in the TRNv of the lesioned side in comparison to the normal, non-lesioned side¹⁰. c) Neurochemical (HPLC) results¹¹ showed significant increased levels of glutamate and GABA in LGN but not in MGN of rats that explored a NCE with respect to controls, consistent with increased glutamatergic cortical inputs and GABAergic TRN inputs to LGN but not to MGN induced by exploration. Altogether, these results provide strong evidence for dependence of attentional activation of TRNv on ‘top-down’ inputs from the primary visual cortex via corticogeniculate pathways, and suggest that a main function of the corticothalamic pathways to relay thalamic nuclei is attention-dependent modulation of thalamocortical transmission

Further questions on neural mechanisms underlying attentional activation of the corticogeniculate pathways and TRNv, and of its functional implications, are being investigated.

Selected Publications

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1. Montero, V. M., Guillery, R. W. and Woolsey, C. N. (1977) Retinotopic organization within the thalamic reticular nucleus demonstrated by a double label autoradiographic technique, Brain Res. 138: 407-421, 1977.
    
2. Montero, V. M. and Scott, G. L. (1981) Synaptic terminals in the dorsal lateral geniculate nucleus from neurons of the thalamic reticular neurons: a light and electron microscope autoradiographic study, Neuroscience 6: 2561-2577.
    
3. Montero, V. M. (1983) Ultrastructural identification of axon terminals from the thalamic reticular nucleus in the medial geniculate body in the rat: An EM autoradiographic study. Exp. Brain Res. 51: 338-342
    
4. Montero, V. M. and Singer, W. (1984) Ultrastructure and synaptic relations of neural elements containing glutamic acid decarboxylase (GAD) in the perigeniculate nucleus of the cat: A light and electron microscopy immunocytochemical study, Exp. Brain Res. 56: 115-125.
    
5. Montero, V. M. (1989) Ultrastructural identification of synaptic terminals from cortical axons and from collateral axons of geniculo-cortical relay cells in the perigeniculate nucleus of the cat. Exp. Brain Res. 75: 65-72.
    
6. Montero, V. M. and Wenthold, R. J. (1989) Quantitative immunogold analysis reveals high glutamate levels in retinal and cortical synaptic terminals in the lateral geniculate nucleus of the macaque. Neuroscience 31: 639-647.
    
7. Montero, V. M., and Shi J. (1995) Induction of c-fos protein by patterned visual stimulation in central visual pathways of the rat. Brain Research 690: 189-199.
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8. Montero, V. M. (1997) C-fos induction in sensory pathways of rats exploring a novel complex environment: Shifts of active thalamic reticular sectors by predominant sensory cues. Neuroscience 76: 1069-1081.
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9. Montero, V. M. (1999) Amblyopia decreases activation of the corticogeniculate pathway and visual thalamic reticularis in attentive rats: A "focal attention" hypothesis. Neuroscience 91:805-817.
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10. Montero, V. M. (2000) Attentional activation of the visual thalamic reticular nucleus depends on 'top-down' inputs from the primary visual cortex via corticogeniculate pathways. Brain Research 864: 95-104.
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11. Montero, V. M., Wright, L.S. and Siegel, F. (2001) Increased glutamate, GABA and glutamine in lateral geniculate nucleus but not in medial geniculate nucleus caused by visual attention to novelty. Brain Research 916: 152-158.
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