Final Report Summary - SENSORY THALAMUS (Thalamic sensory processing during different behaviours)
Project context and objectives
Sensory information is actively acquired. We move our eyes to examine points of interest in a visual scene and we move our fingers across surfaces to perceive the shape and texture of objects. Tactile perception therefore emerges as the result of active exploration. A central issue in sensory physiology is to understand how an animal endowed with highly sensitive sensory organs, whilst exploring the environment, can control the unceasing stream of sensory inputs it receives, and select those that are most relevant to an adaptive behaviour. In rodents, active somatosensory perception is particularly relevant through rhythmic and rapid sweeps of facial whiskers contacting objects in the surrounding environment. Due to the morphological arrangement of each of its major component parts, the vibrissal system of rodents has become a valuable model for research in sensory physiology. Faithful transmission of whisker-related sensory information from the periphery to the neocortex is thought to occur through the ventroposteromedial thalamic nucleus (VPM). On the other hand, neurons of the posterior group of the thalamus (Po), the other major somatosensory thalamic nucleus, respond weakly to whisker stimuli because they receive strong and rapid inhibitory inputs from the zona incerta arriving before excitatory inputs from the brainstem.
The type of information encoded by each of these pathways is still poorly understood. Clearly, there should exist multilevel, state-dependent and context-dependent information coding by the different vibrissal pathways. Five years ago, when we drew up this project, our knowledge of thalamic processing in the whisker sensorimotor system was largely based on recordings from anesthetised rats. To uncover the functional relevance of these parallel sensory pathways, there was then a crucial need to make measurements in wakeful animals during whisker-related behaviour and the present project addressed this issue.
Work performed
Thanks to the financial support from the EU research grant , we developed a technical approach to perform, in the wakeful and behaving mouse, intra- and extracellular single-unit recordings in the somatosensory thalamus coupled with local field potential recordings in primary somatosensory barrel cortex and video-tracking of whisker movements. To our knowledge, this was the first study of the thalamic membrane dynamics across the sleep-wake cycle and the whiskered behaviour of a mouse.
Main results
Thalamic function during active whisker sensing in head-restrained mice
Single-unit recordings showed a significant increase of VPM cells activity during whiskered behaviour; in contrast, such an increase is rather moderate or absent in Po cells. Intracellular recordings revealed inhibitory inputs in some Po neurons immediately preceding the onset of whisker movement. We therefore performed single-units recordings in the ventral part of zona incerta, which receives trigeminal inputs and sends inhibitory outputs to Po cells, and found evidence for a strong increase in the activity of these incertal cells in the 300 ms preceding whisker movement. Maximal incertal firing was recorded at the onset of whisker movement, but slowed down and returned to baseline before the offset of whisker movement. This inhibitory gating on Po cells by the zona incerta may therefore occur at a crucial time to shut down suboptimal sensory information due to whisker movement per se.
Thalamic firing and membrane dynamics across the sleep-wake cycle in mice
Little is known about thalamic cell activity across the natural sleep-wake cycle, nor its correlates with neocortical activity in non-anesthetised animals. We therefore took advantage of our recordings in non-anesthetised mice to address this issue. We observed that while tonically active during whisker movements, thalamic cells strongly decreased their firing during quiet wakefulness. In slow wave sleep, thalamic cells exhibited robust bursts correlated with the cortical waves, and their membrane potential was more hyperpolarised than in wakefulness and characterised by 1-10 mV membrane potential oscillations correlated with cortical slow waves and spindles. When the mouse entered paradoxical sleep (REM sleep), thalamic neurons were suddenly depolarised and increased their firing rate. Most cells further increased their activity simultaneously with the REM-sleep-associated whisker movements and cortical desynchronisation.
This study is the first characterisation of rodent thalamic membrane dynamics across physiological sleep and wakefulness. Although cortical response to whisker behaviour had been described, our results bridge the gap between periphery and cortex. Our data reveals that thalamic membrane potential and/or firing is strongly responsive to peripheral inputs, but also tightly linked with cortical activity in each vigilant state. This original data is therefore crucial for the understanding of information processing throughout the somatosensory system. We have evidence that the putative inhibitory gating from the zona incerta on Po cells occurs at a crucial time to shut down suboptimal sensory information due to whisker movement per se and may therefore sharpen selectivity for reliable stimulus identification.
Socio-economic impact of the project
Combining sharp recordings of thalamic cells membrane potential in awake mice while recording whisker-related behaviour provided the 'state of the art' from which to explore the somatosensory system processing. This had never been done before. The accomplishment of this project improves firstly our knowledge of the somatosensory system, and secondly promotes the progress of technology, because nothing similar had been done deep in the brain. We met the challenge by adapting our tools. Our results provide fundamental knowledge concerning how the brain processes sensory information. Understanding coding in the brain is an essential prerequisite to therapy based on brain-machine interfacing and therapy of complex brain disorders, like epilepsy, schizophrenia and autism.
This project is therefore increasing and strengthening the competitiveness and innovative capacity of the European fundamental research. We are strongly committed to European research and think that the current frontiers in neuroscience should be explored within Europe. Research in Europe is of great importance, both at the level of health (where brain-related diseases are making an increasingly large economic and social burden) and at the level of education (where our future prosperity clearly relates to a highly skilled and educated workforce).
Sensory information is actively acquired. We move our eyes to examine points of interest in a visual scene and we move our fingers across surfaces to perceive the shape and texture of objects. Tactile perception therefore emerges as the result of active exploration. A central issue in sensory physiology is to understand how an animal endowed with highly sensitive sensory organs, whilst exploring the environment, can control the unceasing stream of sensory inputs it receives, and select those that are most relevant to an adaptive behaviour. In rodents, active somatosensory perception is particularly relevant through rhythmic and rapid sweeps of facial whiskers contacting objects in the surrounding environment. Due to the morphological arrangement of each of its major component parts, the vibrissal system of rodents has become a valuable model for research in sensory physiology. Faithful transmission of whisker-related sensory information from the periphery to the neocortex is thought to occur through the ventroposteromedial thalamic nucleus (VPM). On the other hand, neurons of the posterior group of the thalamus (Po), the other major somatosensory thalamic nucleus, respond weakly to whisker stimuli because they receive strong and rapid inhibitory inputs from the zona incerta arriving before excitatory inputs from the brainstem.
The type of information encoded by each of these pathways is still poorly understood. Clearly, there should exist multilevel, state-dependent and context-dependent information coding by the different vibrissal pathways. Five years ago, when we drew up this project, our knowledge of thalamic processing in the whisker sensorimotor system was largely based on recordings from anesthetised rats. To uncover the functional relevance of these parallel sensory pathways, there was then a crucial need to make measurements in wakeful animals during whisker-related behaviour and the present project addressed this issue.
Work performed
Thanks to the financial support from the EU research grant , we developed a technical approach to perform, in the wakeful and behaving mouse, intra- and extracellular single-unit recordings in the somatosensory thalamus coupled with local field potential recordings in primary somatosensory barrel cortex and video-tracking of whisker movements. To our knowledge, this was the first study of the thalamic membrane dynamics across the sleep-wake cycle and the whiskered behaviour of a mouse.
Main results
Thalamic function during active whisker sensing in head-restrained mice
Single-unit recordings showed a significant increase of VPM cells activity during whiskered behaviour; in contrast, such an increase is rather moderate or absent in Po cells. Intracellular recordings revealed inhibitory inputs in some Po neurons immediately preceding the onset of whisker movement. We therefore performed single-units recordings in the ventral part of zona incerta, which receives trigeminal inputs and sends inhibitory outputs to Po cells, and found evidence for a strong increase in the activity of these incertal cells in the 300 ms preceding whisker movement. Maximal incertal firing was recorded at the onset of whisker movement, but slowed down and returned to baseline before the offset of whisker movement. This inhibitory gating on Po cells by the zona incerta may therefore occur at a crucial time to shut down suboptimal sensory information due to whisker movement per se.
Thalamic firing and membrane dynamics across the sleep-wake cycle in mice
Little is known about thalamic cell activity across the natural sleep-wake cycle, nor its correlates with neocortical activity in non-anesthetised animals. We therefore took advantage of our recordings in non-anesthetised mice to address this issue. We observed that while tonically active during whisker movements, thalamic cells strongly decreased their firing during quiet wakefulness. In slow wave sleep, thalamic cells exhibited robust bursts correlated with the cortical waves, and their membrane potential was more hyperpolarised than in wakefulness and characterised by 1-10 mV membrane potential oscillations correlated with cortical slow waves and spindles. When the mouse entered paradoxical sleep (REM sleep), thalamic neurons were suddenly depolarised and increased their firing rate. Most cells further increased their activity simultaneously with the REM-sleep-associated whisker movements and cortical desynchronisation.
This study is the first characterisation of rodent thalamic membrane dynamics across physiological sleep and wakefulness. Although cortical response to whisker behaviour had been described, our results bridge the gap between periphery and cortex. Our data reveals that thalamic membrane potential and/or firing is strongly responsive to peripheral inputs, but also tightly linked with cortical activity in each vigilant state. This original data is therefore crucial for the understanding of information processing throughout the somatosensory system. We have evidence that the putative inhibitory gating from the zona incerta on Po cells occurs at a crucial time to shut down suboptimal sensory information due to whisker movement per se and may therefore sharpen selectivity for reliable stimulus identification.
Socio-economic impact of the project
Combining sharp recordings of thalamic cells membrane potential in awake mice while recording whisker-related behaviour provided the 'state of the art' from which to explore the somatosensory system processing. This had never been done before. The accomplishment of this project improves firstly our knowledge of the somatosensory system, and secondly promotes the progress of technology, because nothing similar had been done deep in the brain. We met the challenge by adapting our tools. Our results provide fundamental knowledge concerning how the brain processes sensory information. Understanding coding in the brain is an essential prerequisite to therapy based on brain-machine interfacing and therapy of complex brain disorders, like epilepsy, schizophrenia and autism.
This project is therefore increasing and strengthening the competitiveness and innovative capacity of the European fundamental research. We are strongly committed to European research and think that the current frontiers in neuroscience should be explored within Europe. Research in Europe is of great importance, both at the level of health (where brain-related diseases are making an increasingly large economic and social burden) and at the level of education (where our future prosperity clearly relates to a highly skilled and educated workforce).