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- Wärnberg, Emil
(författare)
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On learning in mice and machines : continuous population codes in natural and artificial neural networks
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neural networks, whether artificial in a computer or natural in the brain, could represent information either using discrete symbols or continuous vector spaces. In this thesis, I explore how neural networks can represent continuous vector spaces, using both simulated neural networks and analysis of real neural population data recorded from mice. A special focus is on the networks of the basal ganglia circuit and on reinforcement learning, i.e., learning from rewards and punishments.The thesis includes four scientific papers: two theoretical/computational (Papers I and IV) and two with analysis of real data (Papers II and III).In Paper I, we explore methods for implementing continuous vector spaces in networks of spiking neurons using multidimensional attractors, and propose an explanation for why it is hard to escape the neural manifolds created by such attractors.In Paper II, we analyze experimental data from dorsomedial striatum collected using 1-photon calcium imaging of transgenic mice with celltype-specific markers for the striatal direct, indirect and patch pathways, as the mice were gathering rewards in a 2-choice task. In line with extensive previous results, our data analysis revealed a number of neural signatures of reinforcement learning, but no apparent difference between the pathways.In Paper III, we present a new software tool for tracking neurons across weeks of 1-photon calcium imaging, and employ it to follow patch-specific striatal projection neurons from the dorsomedial striatum across two weeks of daily recordings.In Paper IV, we propose a model for how the nigrostriatal dopaminergic projection could, in a biologically plausible way, convey a vector-valued error gradient to the dorsal striatum, as required for backpropagation.Based on the results of the papers and a review of existing literature, I argue that while the basal ganglia indeed make up a circuit for reinforcement learning as previously thought, this circuit represents reinforcement learning states, actions and policies using a continuous population code and not using discrete symbols.
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| 2. |
- Guillaumin, Adriane
(författare)
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The subthalamic nucleus in motor and affective functions : An optogenetic in vivo-investigation
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The basal ganglia form a group of subcortical interconnected nuclei involved in motor, limbic and cognitive functions. According to the classical model of the basal ganglia, two main pathways exert opposing control over movement, one facilitating movement and the other suppressing movement. The subthalamic nucleus (STN) plays a critical role in this function, and has also been implicated in reward processing. Despite ample knowledge of the role of the STN in motor dysfunctions in relation to Parkinson’s disease, less is known about STN’s natural role in healthy subjects.The studies described in this thesis aimed to address the functional role of the STN in its natural neurocircuitry by using a transgenic mouse line which expresses Cre recombinase under the Pitx2 promoter. The Pitx2 gene is restricted to the STN and the use of Pitx2-Cre mice thereby allows selective manipulation of STN neurons by using optogenetics. By expressing Channelrhodopsin (ChR2) or Archaerhodopsin (Arch) in Pitx2-Cre neurons, we could optogenetically excite or inhibit STN Pitx2-Cre neurons and investigate the role of the STN in motor and affective functions. We showed that optogenetic inhibition and excitation of the STN induce opposite effects on motor activity. STN excitation reduced locomotion while STN inhibition enhanced locomotion, thereby providing experimental evidence to classical motor models postulating this role. We also showed that optogenetic excitation of the STN induces potent place avoidance, a behaviour relevant to aversion. Projections from the STN to the ventral pallidum (VP) exist that when excited induced the same behaviour. The VP projects to the lateral habenula (LHb), a structure known for its role in aversion. A glutamatergic multi-synaptic connection between the STN and the LHb was confirmed.Aversive behaviour is also mediated by the hypothalamic-mesencephalic area. The Trpv1 gene is expressed within the posterior hypothalamus. By applying optogenetics in a Trpv1-Cre mouse line, projection patterns to limbic brain areas were identified, and optogenetic excitation of Trpv1-Cre neurons was found to induce place avoidance.The STN and posterior hypothalamus are thereby demonstrated as new players in the aversion neurocircuitry, while the long-assumed role of the STN in motor behaviour is confirmed. To enable future analyses of how STN manipulation might rescue motor and affective deficiency relevant to human disorders, a neuronal degeneration mouse model was generated.To conclude, the results presented in this thesis contribute to enhanced neurobiological understanding of the role played by the STN in motor and affective functions.
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