Evolution of the subcortical circuits controlling goal-directed behaviour
Author: Stephenson-Jones, Marcus
Date: 2012-09-14
Location: Hillarpsalen, Retzius väg 8, Karolinska Institutet, Solna
Time: 09.00
Department: Inst för neurovetenskap / Dept of Neuroscience
Abstract
The aim of the work presented in this thesis was to reconstruct the minimal neural hardware that vertebrates use for goal-directed behaviour. By studying lamprey, one of the phylogenetically oldest vertebrates, we were able to identify the neural circuitry that has been conserved since jawed and jawless vertebrates diverged over 560 million years ago. Specifically we examined the conservation of the subcortical circuits involving the optic tectum, basal ganglia and habenula. These structures are responsible for steering, action selection and motivation in mammals.
Optic tectum; this structure is essential for visually guiding purposeful movements to either avoid or approach objects of interest. Using a combination of tract tracing and stereology we demonstrated that the pattern of sensory innervation is conserved as the retinotectal connection in lamprey is arranged in a retinotopic manner. By analyzing the spatial arrangement between this retinotopic map and the underlying motor map (Saitoh et al., 2007) we revealed that optic tectum can guide lamprey towards or away from the source of visual input. This suggests that tectal circuits controlling both approach and avoidance were present at the dawn of vertebrate evolution and have subsequently been conserved. Furthermore, our result indicate that there are two independent retinal circuits in lamprey; one that may contact the photoreceptors directly and transmit information to the pretectum with a minimal delay for reflexive behaviours and another that contacts the image forming part of the retina (inner plexiform layer) that sends projections to the optic tectum to control goal-directed visual behaviours.
Basal ganglia; these nuclei play a key role in action selection in mammals. We showed, using immunohistochemistry, tract tracing, and whole-cell recordings, that all parts of the mammalian basal ganglia (striatum, globus pallidus interna [GPi] and externa [GPe], and subthalamic nucleus [STN]) are present in the lamprey forebrain. In addition, the circuit features, molecular markers, and physiological activity patterns are conserved. Thus, GABAergic striatal neurons expressing substance P project directly to the pallidal output layer, whereas enkephalin-expressing striatal neurons project indirectly via nuclei homologous to the GPe and STN. These results show for the first time that both the “direct” and “indirect” pathways are present in a lower (anamniote) vertebrate. Our results suggest that this circuitry has been conserved in all vertebrates, most likely as a mechanism for action selection, for over 560 million years. Extending our analysis we revealed that the phylogenetically oldest basal ganglia include the pedunculopontine nucleus and a separate habenula projecting pallidal nucleus. This later nucleus differs from other pallidal nuclei, as its neurons project to a reward-related structure, are glutamatergic and differ from other pallidal neurons in their molecular expression, connectivity and electrophysiological properties. These results suggest that this nucleus may represent the output of a previously unappreciated pathway through the basal ganglia.
Habenulae; the medial (MHb) and lateral (LHb) habenulae are a small group of nuclei that contribute to a range of cognitive and motor functions by regulating the neuromodulatory systems. Based on connectivity and molecular expression, we show that the MHb and LHb circuitry is conserved in the lamprey. As in mammals, neurons in the LHb homolog project indirectly to dopamine and serotonin neurons through a nucleus homologous to the GABAergic rostromedial mesopontine tegmental nucleus. This suggests that the LHb may exert an inhibitory influence on the neuromodulatroy systems to regulate reinforcement learning and motivation as it does in mammals. The efferents of the MHb homolog selectively target the interpeduncular nucleus, which in turn projects to regions involved in innate behavioral responses such as fight or flight. In contrast to mammals, the MHb afferents arise from sensory (medial olfactory bulb, parapineal, and pretectum) and not limbic areas. This suggests that the “context” in which this circuitry is recruited but not the role of the circuit may have changed during evolution. Our results indicate that the habenular nuclei provide a common vertebrate circuitry to adapt behavior in response to rewards, stress, and other motivating factors.
Optic tectum; this structure is essential for visually guiding purposeful movements to either avoid or approach objects of interest. Using a combination of tract tracing and stereology we demonstrated that the pattern of sensory innervation is conserved as the retinotectal connection in lamprey is arranged in a retinotopic manner. By analyzing the spatial arrangement between this retinotopic map and the underlying motor map (Saitoh et al., 2007) we revealed that optic tectum can guide lamprey towards or away from the source of visual input. This suggests that tectal circuits controlling both approach and avoidance were present at the dawn of vertebrate evolution and have subsequently been conserved. Furthermore, our result indicate that there are two independent retinal circuits in lamprey; one that may contact the photoreceptors directly and transmit information to the pretectum with a minimal delay for reflexive behaviours and another that contacts the image forming part of the retina (inner plexiform layer) that sends projections to the optic tectum to control goal-directed visual behaviours.
Basal ganglia; these nuclei play a key role in action selection in mammals. We showed, using immunohistochemistry, tract tracing, and whole-cell recordings, that all parts of the mammalian basal ganglia (striatum, globus pallidus interna [GPi] and externa [GPe], and subthalamic nucleus [STN]) are present in the lamprey forebrain. In addition, the circuit features, molecular markers, and physiological activity patterns are conserved. Thus, GABAergic striatal neurons expressing substance P project directly to the pallidal output layer, whereas enkephalin-expressing striatal neurons project indirectly via nuclei homologous to the GPe and STN. These results show for the first time that both the “direct” and “indirect” pathways are present in a lower (anamniote) vertebrate. Our results suggest that this circuitry has been conserved in all vertebrates, most likely as a mechanism for action selection, for over 560 million years. Extending our analysis we revealed that the phylogenetically oldest basal ganglia include the pedunculopontine nucleus and a separate habenula projecting pallidal nucleus. This later nucleus differs from other pallidal nuclei, as its neurons project to a reward-related structure, are glutamatergic and differ from other pallidal neurons in their molecular expression, connectivity and electrophysiological properties. These results suggest that this nucleus may represent the output of a previously unappreciated pathway through the basal ganglia.
Habenulae; the medial (MHb) and lateral (LHb) habenulae are a small group of nuclei that contribute to a range of cognitive and motor functions by regulating the neuromodulatory systems. Based on connectivity and molecular expression, we show that the MHb and LHb circuitry is conserved in the lamprey. As in mammals, neurons in the LHb homolog project indirectly to dopamine and serotonin neurons through a nucleus homologous to the GABAergic rostromedial mesopontine tegmental nucleus. This suggests that the LHb may exert an inhibitory influence on the neuromodulatroy systems to regulate reinforcement learning and motivation as it does in mammals. The efferents of the MHb homolog selectively target the interpeduncular nucleus, which in turn projects to regions involved in innate behavioral responses such as fight or flight. In contrast to mammals, the MHb afferents arise from sensory (medial olfactory bulb, parapineal, and pretectum) and not limbic areas. This suggests that the “context” in which this circuitry is recruited but not the role of the circuit may have changed during evolution. Our results indicate that the habenular nuclei provide a common vertebrate circuitry to adapt behavior in response to rewards, stress, and other motivating factors.
List of papers:
I. Jones MR, Grillner S, Robertson B. Selective projection patterns from subtypes of retinal ganglion cells to tectum and pretectum: distribution and relation to behaviour. J Comp Neurol. 2009 Nov 517:257-75.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Stephenson-Jones M, Samuelsson E, Ericsson J, Robertson B, Grillner S. Evolutionary conservation of the basal ganglia as a common vertebrate mechanism for action selection. Curr Bio. 2011 Jul 21:1081-91.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Stephenson-Jones M, Ericsson J, Robertson B, Grillner S. Evolution of the basal ganglia: dual output pathways conserved throughout vertebrate phylogeny. J Comp Neurol. 2012 Sep 520:2957-73.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Stephenson-Jones M, Floros O, Robertson B, Grillner S. Evolutionary conservation of the habenular nuclei and their circuitry controlling the dopamine and 5-hydroxytryptophan (5-HT) systems. Proc Natl Acad Sci U S A. 2012 Jan 109:E164-73.
Fulltext (DOI)
Pubmed
View record in Web of Science®
V. Stephenson-Jones M, Kardamakis A, Grillner S. Habenula and Thalamic Projecting Pallidal Neurons are the Output of Separate Independent Basal Ganglia Circuits. [Manuscript]
I. Jones MR, Grillner S, Robertson B. Selective projection patterns from subtypes of retinal ganglion cells to tectum and pretectum: distribution and relation to behaviour. J Comp Neurol. 2009 Nov 517:257-75.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Stephenson-Jones M, Samuelsson E, Ericsson J, Robertson B, Grillner S. Evolutionary conservation of the basal ganglia as a common vertebrate mechanism for action selection. Curr Bio. 2011 Jul 21:1081-91.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Stephenson-Jones M, Ericsson J, Robertson B, Grillner S. Evolution of the basal ganglia: dual output pathways conserved throughout vertebrate phylogeny. J Comp Neurol. 2012 Sep 520:2957-73.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Stephenson-Jones M, Floros O, Robertson B, Grillner S. Evolutionary conservation of the habenular nuclei and their circuitry controlling the dopamine and 5-hydroxytryptophan (5-HT) systems. Proc Natl Acad Sci U S A. 2012 Jan 109:E164-73.
Fulltext (DOI)
Pubmed
View record in Web of Science®
V. Stephenson-Jones M, Kardamakis A, Grillner S. Habenula and Thalamic Projecting Pallidal Neurons are the Output of Separate Independent Basal Ganglia Circuits. [Manuscript]
Institution: Karolinska Institutet
Supervisor: Grillner, Sten
Issue date: 2012-08-24
Rights:
Publication year: 2012
ISBN: 978-91-7457-852-2
Statistics
Total Visits
Views | |
---|---|
Evolution ...(legacy) | 892 |
Evolution ... | 175 |
Total Visits Per Month
September 2023 | October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | |
---|---|---|---|---|---|---|---|
Evolution ... | 0 | 2 | 1 | 3 | 1 | 0 | 1 |
File Visits
Views | |
---|---|
Thesis_Marcus_Stephenson-Jones.pdf(legacy) | 544 |
Thesis_Marcus_Stephenson-Jones.pdf | 397 |
Spikblad_Marcus_Stephenson-Jones.pdf(legacy) | 197 |
Spikblad_Marcus_Stephenson-Jones.pdf | 33 |
Spikblad_Marcus_Stephenson-Jones.pdf.txt(legacy) | 4 |
Thesis_Marcus_Stephenson-Jones.pdf.txt(legacy) | 4 |
Avhandling Marcus Jones.pdf(legacy) | 1 |
Avhandling_omslag_Marcus Silk 350g OK.pdf(legacy) | 1 |
Top country views
Views | |
---|---|
United States | 398 |
Germany | 125 |
Sweden | 88 |
China | 66 |
United Kingdom | 36 |
Japan | 24 |
Vietnam | 17 |
Denmark | 16 |
South Korea | 16 |
France | 11 |
Top cities views
Views | |
---|---|
Ashburn | 50 |
Kiez | 49 |
Romeo | 40 |
Stockholm | 38 |
Sunnyvale | 24 |
Tokyo | 22 |
London | 18 |
Beijing | 17 |
Frankfurt Am Main | 16 |
Seoul | 16 |