| 1. |
- Hjorth, J. J. Johannes, et al.
(författare)
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The microcircuits of striatum in silico
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:17, s. 9554-9565
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Tidskriftsartikel (refereegranskat)abstract
- The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, somadendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.
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| 2. |
- Lindroos, Robert, 1980-, et al.
(författare)
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Perceptual odor qualities predict successful odor identification in old age
- 2022
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 47
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Tidskriftsartikel (refereegranskat)abstract
- Odor identification is a common assessment of olfaction, and it is affected in a large number of diseases. Identification abilities decline with age, but little is known about whether there are perceptual odor features that can be used to predict identification. Here, we analyzed data from a large, population-based sample of 2,479 adults, aged 60 years or above, from the Swedish National study on Aging and Care in Kungsholmen. Participants performed both free and cued odor identification tests. In a separate experiment, we assessed perceived pleasantness, familiarity, intensity, and edibility of all odors in the first sample, and examined how odor identification performance is associated with these variables. The analysis showed that high-intensity odors are easier to identify than low-intensity odors overall, but also that they are more susceptible to the negative repercussions of old age. This result indicates that sensory decline is a major aspect of age-dependent odor identification impairment, and suggests a framework where identification likelihood is proportional to the perceived intensity of the odor. Additional analyses further showed that high-performing individuals can discriminate target odors from distractors along the pleasantness and edibility dimensions and that unpleasant and inedible odors show smaller age-related differences in identification. Altogether, these results may guide further development and optimization of brief and efficient odor identification tests as well as influence the design of odorous products targeted toward older consumers.
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| 3. |
- Lindroos, Robert
(författare)
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The role of dopaminergic and cholinergic modulation on the striatal network : a computational investigation
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The famous words from the French philosopher René Descartes (1596-1650), “I think therefore I am”, proclaims that since we are thinking we must also exist. At the time when this was stated, very little was known about the main organ involved in thinking, the nervous system. Today we know that the nervous system consists of interconnected cells, so called neurons that communicate with each other through electro-chemical signals. This has been known for little over a century and during this time we have gathered an impressive amount of detailed data on neurons and the circuits they make up. Despite this, we still don’t have a detailed description of the overall computing mechanism of the central nervous system, the brain, or even single nuclei within the brain. One reason for this is the transient nature of the brain, continuously going in and out of operational modes, or so called brain states. The state of the brain is heavily influenced by neuromodulators – molecules changing the properties of neurons and the connections between them. One area strongly affected by neuromodulators is the striatum, the main input structure of the basal ganglia. The basal ganglia are an evolutionary conserved set of interconnected nuclei tightly connected to the cerebral cortex and thalamus, with which they form a loop. From pathological states like Parkinson’s disease we know that the basal ganglia are involved in motor control. More specifically they have been proposed to drive formation and control of automatic motor response sequences (including habits), but like in the rest of the brain, the modus operandi of the basal ganglia is not known. To bridge the gap between data and function we therefore need models and testable theories. In this thesis I have studied the role of neuromodulation in the striatal microcircuit, with the aim of understanding how subcellular changes affect cellular behavior. The technique used is biophysically detailed computational modelling. The essence of these models tries to mimic the electro-chemical signals within and between neurons using as detailed a description of individual neurons as possible. From this standpoint a good model minimizes the number of assumptions used in construction, by restricting the model to experimentally measured entities. Simulations of the striatal projection neurons in such models show that complex spikes – a particular type of neuronal signal associated with learning in other brain regions – may be triggered following manipulation of certain conductances in the cell membrane. In our simulations, the complex spikes were associated with large calcium signals in the dendrites, indicating a more robust form of crosstalk in the soma-to-dendrites direction than following regular action potentials. Together these simulations extend the theory of striatal function and learning.
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| 4. |
- Raj, Rohan, 1996-, et al.
(författare)
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Odor identification errors reveal cognitive aspects of age-associated smell loss
- 2023
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Ingår i: Cognition. - : Elsevier. - 0010-0277 .- 1873-7838. ; 236
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Tidskriftsartikel (refereegranskat)abstract
- Human olfaction can be extraordinarily sensitive, and its most common assessment method is odor identification (OID), where everyday odors are matched to word labels in a multiple-choice format. However, many older persons are unable to identify familiar odors, a deficit that is associated with the risk of future dementia and mortality. The underlying processes subserving OID in older adults are poorly understood. Here, we analyzed error patterns in OID to test whether errors could be explained by perceptual and/or semantic similarities among the response alternatives. We investigated the OID response patterns in a large, population-based sample of older adults in Sweden (n = 2479; age 60–100 years). Olfaction was assessed by a ‘Sniffin ́ TOM OID test with 16 odors; each trial involved matching a target odor to a correct label among three distractors. We analyzed the pattern of misidentifications, and the results showed that some distractors were more frequently selected than others, suggesting cognitive or perceptual factors may be present. Relatedly, we conducted a large online survey of older adults (n = 959, age 60–90 years) who were asked to imagine and rate the perceptual similarity of the target odors and the three corresponding distractors (e.g. “How similar are these smells: apple and mint?”). We then used data from the Swedish web corpus and the Word2Vec neural network algorithm to quantify the semantic association strength between the labels of each target odor and its three distractors. These data sources were used to predict odor identification errors. We found that the error patterns were partly explained by both the semantic similarity between target-distractor pairs, and the imagined perceptual similarity of the target-distractor pair. Both factors had, however, a diminished prediction in older ages, as responses became gradually less systematic. In sum, our results suggest that OID tests not only reflect olfactory perception, but also likely involve the mental processing of odor-semantic associations. This may be the reason why these tests are useful in predicting dementia onset. Our insights into olfactory-language interactions could be harnessed to develop new olfactory tests that are tailored for specific clinical purposes.
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