A basal forebrain to midbrain circuit drives exploratory locomotion
A basal forebrain to midbrain circuit drives exploratory locomotion
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Date of Embargo
01.11.2025Type of Scholarly Publication
DissertationDate of Exam
17.10.2023Date of Publication
26.10.2023Advisor
Remy, StefanCo-Referee
Isbrandt, DirkMetadata
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Abstract
Locomotion is a fundamental behavior that comprises different specialized neuronal networks. In the basal forebrain, the glutamatergic neurons of the medial septum and diagonal band of Broca (MSDBglu) can initiate locomotion and control its speed when optogenetically stimulated. MSDBglu neuronal activity is also linked to hippocampal theta oscillations and codes for aversive salient stimuli. This work aims at investigating the downstream target of the MSDBglu neurons responsible for the locomotor effect, and the underlying motivation that brings animals to move upon the activation of this circuit. Tracing studies identified the ventral tegmental area (VTA) as a candidate region receiving MSDBglu inputs. Combining retrograde tracing, slice electrophysiology, in vivo fiberphotometry, pharmacology, and optogenetics, my aim was to understand the role of MSDBglu projections to VTA during rodents’ behavior in both head-fixed and freely moving tasks. Unsupervised machine learning methods allowed me to extract the animal’s pose dynamics and quantify the effect of the network manipulation on behavior at a sub-second time scale.
Tracing and in vitro patch-clamp data confirmed the existence of a monosynaptic glutamatergic connection between MSDB and VTA, and highlighted how MSDBglu inputs target a heterogeneous population of VTA neurons. Optogenetic activation of MSDBglu axons in VTA was sufficient to induce locomotion and to control its speed in a frequency-dependent manner. Lidocaine infusion in the MSDB did not affect the results of the optogenetic stimulation, thus identifying the VTA as a downstream region in the locomotor circuit initiated in the MSDB. These findings were further supported by the increase in calcium signals of MSDBglu axons in VTA when animals were spontaneously moving. I found that MSDBglu-VTA circuit activation causes an increase of sniffing and whisking prior to locomotion initiation on the treadmill, and leads to a higher representation of rearing motifs in the open field, all actions classically linked to exploration.
Taken together, in the present work I investigated the MSDBglu neurons and their projections to VTA, and unveiled a new role for this subcortical network in promoting exploratory and information-seeking behavior.
Tracing and in vitro patch-clamp data confirmed the existence of a monosynaptic glutamatergic connection between MSDB and VTA, and highlighted how MSDBglu inputs target a heterogeneous population of VTA neurons. Optogenetic activation of MSDBglu axons in VTA was sufficient to induce locomotion and to control its speed in a frequency-dependent manner. Lidocaine infusion in the MSDB did not affect the results of the optogenetic stimulation, thus identifying the VTA as a downstream region in the locomotor circuit initiated in the MSDB. These findings were further supported by the increase in calcium signals of MSDBglu axons in VTA when animals were spontaneously moving. I found that MSDBglu-VTA circuit activation causes an increase of sniffing and whisking prior to locomotion initiation on the treadmill, and leads to a higher representation of rearing motifs in the open field, all actions classically linked to exploration.
Taken together, in the present work I investigated the MSDBglu neurons and their projections to VTA, and unveiled a new role for this subcortical network in promoting exploratory and information-seeking behavior.
Classification (DDC)
610 Medizin, Gesundheit 570 Biowissenschaften, BiologieMocellin, Petra: A basal forebrain to midbrain circuit drives exploratory locomotion. - Bonn, 2023. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-72912
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-72912
@phdthesis{handle:20.500.11811/11109,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-72912,
doi: https://doi.org/10.48565/bonndoc-149,
author = {{Petra Mocellin}},
title = {A basal forebrain to midbrain circuit drives exploratory locomotion},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2023,
month = oct,
note = {Locomotion is a fundamental behavior that comprises different specialized neuronal networks. In the basal forebrain, the glutamatergic neurons of the medial septum and diagonal band of Broca (MSDBglu) can initiate locomotion and control its speed when optogenetically stimulated. MSDBglu neuronal activity is also linked to hippocampal theta oscillations and codes for aversive salient stimuli. This work aims at investigating the downstream target of the MSDBglu neurons responsible for the locomotor effect, and the underlying motivation that brings animals to move upon the activation of this circuit. Tracing studies identified the ventral tegmental area (VTA) as a candidate region receiving MSDBglu inputs. Combining retrograde tracing, slice electrophysiology, in vivo fiberphotometry, pharmacology, and optogenetics, my aim was to understand the role of MSDBglu projections to VTA during rodents’ behavior in both head-fixed and freely moving tasks. Unsupervised machine learning methods allowed me to extract the animal’s pose dynamics and quantify the effect of the network manipulation on behavior at a sub-second time scale.
Tracing and in vitro patch-clamp data confirmed the existence of a monosynaptic glutamatergic connection between MSDB and VTA, and highlighted how MSDBglu inputs target a heterogeneous population of VTA neurons. Optogenetic activation of MSDBglu axons in VTA was sufficient to induce locomotion and to control its speed in a frequency-dependent manner. Lidocaine infusion in the MSDB did not affect the results of the optogenetic stimulation, thus identifying the VTA as a downstream region in the locomotor circuit initiated in the MSDB. These findings were further supported by the increase in calcium signals of MSDBglu axons in VTA when animals were spontaneously moving. I found that MSDBglu-VTA circuit activation causes an increase of sniffing and whisking prior to locomotion initiation on the treadmill, and leads to a higher representation of rearing motifs in the open field, all actions classically linked to exploration.
Taken together, in the present work I investigated the MSDBglu neurons and their projections to VTA, and unveiled a new role for this subcortical network in promoting exploratory and information-seeking behavior.},
url = {https://hdl.handle.net/20.500.11811/11109}
}
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-72912,
doi: https://doi.org/10.48565/bonndoc-149,
author = {{Petra Mocellin}},
title = {A basal forebrain to midbrain circuit drives exploratory locomotion},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2023,
month = oct,
note = {Locomotion is a fundamental behavior that comprises different specialized neuronal networks. In the basal forebrain, the glutamatergic neurons of the medial septum and diagonal band of Broca (MSDBglu) can initiate locomotion and control its speed when optogenetically stimulated. MSDBglu neuronal activity is also linked to hippocampal theta oscillations and codes for aversive salient stimuli. This work aims at investigating the downstream target of the MSDBglu neurons responsible for the locomotor effect, and the underlying motivation that brings animals to move upon the activation of this circuit. Tracing studies identified the ventral tegmental area (VTA) as a candidate region receiving MSDBglu inputs. Combining retrograde tracing, slice electrophysiology, in vivo fiberphotometry, pharmacology, and optogenetics, my aim was to understand the role of MSDBglu projections to VTA during rodents’ behavior in both head-fixed and freely moving tasks. Unsupervised machine learning methods allowed me to extract the animal’s pose dynamics and quantify the effect of the network manipulation on behavior at a sub-second time scale.
Tracing and in vitro patch-clamp data confirmed the existence of a monosynaptic glutamatergic connection between MSDB and VTA, and highlighted how MSDBglu inputs target a heterogeneous population of VTA neurons. Optogenetic activation of MSDBglu axons in VTA was sufficient to induce locomotion and to control its speed in a frequency-dependent manner. Lidocaine infusion in the MSDB did not affect the results of the optogenetic stimulation, thus identifying the VTA as a downstream region in the locomotor circuit initiated in the MSDB. These findings were further supported by the increase in calcium signals of MSDBglu axons in VTA when animals were spontaneously moving. I found that MSDBglu-VTA circuit activation causes an increase of sniffing and whisking prior to locomotion initiation on the treadmill, and leads to a higher representation of rearing motifs in the open field, all actions classically linked to exploration.
Taken together, in the present work I investigated the MSDBglu neurons and their projections to VTA, and unveiled a new role for this subcortical network in promoting exploratory and information-seeking behavior.},
url = {https://hdl.handle.net/20.500.11811/11109}
}
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