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Lindskog, M.

Publications and source records attributed to Lindskog, M..

5 recordsLinked to original sources

Explicit memory representations in decisions from experience

Reinforcement learning (RL) models explain how people adapt behavior through incremental value updates but assume that individual experiences are not explicitly stored or retrieved. Across two experiments (N = 282 and N = 1,818), we tested whether people rely on such explicit memory representations during experience-based choice. Participants sampled outcomes from two lotteries and, in an "ignore" condition, were instructed to disregard specific outcomes before deciding. Ignoring these outcomes substantially altered preferences, suggesting that choices were guided by explicit episodic representations rather than cumulative reinforcement. Frequency judgments revealed generally accurate memory for experienced outcomes, but reduced precision for continuous compared with discrete outcome distributions. These findings challenge purely incremental RL accounts and support theories proposing that human choice integrates flexible episodic memory with reinforcement mechanisms, bridging models of learning, memory, and decision-making. Statement of RelevanceHow people learn from experience shapes decisions in many everyday situations, from choosing a stock to invest in to selecting a restaurant or deciding which route to take home. Our experiments show that people do not rely solely on incremental value updates but instead exploit memory representations of past outcomes to guide choices. When asked to ignore certain outcomes, participants adjusted their preferences in line with these representations. These findings reveal that human decision-making also engages flexible use of memory for past experiences, highlighting the importance of memory-based mechanisms in adaptive, real-world choice behaviour.

neuroscience↗

GABA-induced Ca2+ signaling in the primary cilium of neurons

The complex signaling processing in neurons requires establishment of autonomous compartments. The compartment that is unique for neurons and crucial for neuron-neuron signaling is the synapse. Another compartment, that neurons share with all other cells in the body, is the primary cilium. The primary cilium is a solitary organelle, present in almost every neuronal cell type, that extends into the extracellular space for detection of signals. Several GPCRs have been identified as ciliary receptors, and here we show that the metabotropic GABA receptor subtype 1 localizes to primary cilia of neurons across different regions of the mouse brain and that activation of these receptors initiates Ca2+ signaling that is restricted to this organelle. The excitatory nature of GABAergic signaling in primary cilia is opposite to GABA action in other neuronal domains, indicating distinct modes of action of this universal inhibitory neurotransmitter even within the same neuron.

neuroscience↗

Effect of ketamine on early synaptic mistuning and emotional behavior deficits in AppNL-F mouse model of Alzheimer's disease.

Alzheimers disease is the most common neurodegenerative disease and constitute 75% of dementia cases worldwide. Unfortunately, efficient and affordable treatments are still lacking for this mental illness, it is therefore urgent to identify new pharmacological targets. Whereas the late phases of the disease are well described, recent evidence suggest synaptic impairments at a pre-amyloid {beta} (A{beta}) plaque stage. Astrocytes are playing a crucial role in the tuning of synaptic transmission and several studies have pointed out severe astrocyte reactivity in Alzheimers disease, especially around A{beta} plaques. Reactive astrocytes show altered physiology and function, suggesting they could have a role in the early pathophysiology of Alzheimers disease. In this study we used the AppNL-F knock-in mouse model of Alzheimers disease which carries two disease-causing mutations inserted in the amyloid precursor protein (App) gene. This strain does not start to develop A{beta} plaques until nine months of age. To better understand early changes in Alzheimers disease, we investigated synaptic function, at both neuronal and astrocytic levels, in six months old AppNL-F mice and correlate the synaptic dysfunction with emotional behavior. Electrophysiological recordings in the hippocampus revealed an overall synaptic mistuning at a pre-plaque stage of the pathology, associated to an intact social memory but a stronger depressive-like behavior. Astrocytes displayed a reactive-like morphology and a higher tonic GABA current compared to control mice. Interestingly, we here show that the synaptic impairments in hippocampal slices are partially corrected by a pre-treatment with the monoamine oxidase B (MAO-B) blocker deprenyl or the fast-acting antidepressant ketamine (5mg/kg). Thus, we propose that reactive astrocytes can induce synaptic mistuning early in Alzheimers disease, before plaques deposition, and that these changes are associated with emotional symptoms. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/540486v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@fb19a7org.highwire.dtl.DTLVardef@151454borg.highwire.dtl.DTLVardef@9c7a12org.highwire.dtl.DTLVardef@112633e_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG

neuroscience↗

Impaired glutamate reuptake induces synaptic mistuning in rat hippocampal slices, that can be counteracted by ketamine

Mistuning of synaptic transmission has been proposed to underlie many psychiatric disorders, with decreased reuptake of the excitatory neurotransmitter glutamate as one contributing factor. Synaptic tuning occurs through several diverging and converging forms of plasticity. By recording evoked field postsynaptic potentials in the CA1 area in hippocampal slices, we found that inhibiting glutamate transporters using DL-TBOA causes retuning of synaptic transmission, resulting in a new steady state with reduced synaptic strength and a lower threshold for inducing long-term synaptic potentiation (LTP). Moreover, we also found reduced threshold for LTP in a rat model of depression that has decreased levels of glutamate transporters. Most importantly, we found that the antidepressant ketamine counteracts the effects of increased glutamate on the various steps involved in synaptic retuning. We therefore propose that ketamines mechanism of action as an antidepressant is to restore adequate synaptic tuning.

neuroscience↗

Grouping effects in numerosity perception under prolonged viewing conditions

Humans can estimate numerosities - such as the number sheep in a flock - without deliberate counting. A number of biases have been identified in these estimates, which seem primarily rooted in the spatial organization of objects (grouping, symmetry, etc). Most previous studies on the number sense used static stimuli with extremely brief exposure times. However, outside the laboratory, visual scenes are often dynamic and freely viewed for prolonged durations (e.g., a flock of moving sheep). The purpose of the present study is to examine grouping-induced numerosity biases in stimuli that more closely mimic these conditions. To this end, we designed two experiments with limited-dot-lifetime displays (LDDs), in which each dot is visible for a brief period of time and replaced by a new dot elsewhere after its disappearance. The dynamic nature of LDDs prevents subjects from counting even when they are free-viewing a stimulus under prolonged presentation. Subjects estimated the number of dots in arrays that were presented either as a single group or were segregated into two groups by spatial clustering, dot size, dot color, or dot motion. Grouping by color and motion reduced perceived numerosity compared to viewing them as a single group. Moreover, the grouping effect sizes between these two features were correlated, which suggests that the effects may share a common, feature-invariant mechanism. Finally, we find that dot size and total stimulus area directly affect perceived numerosity, which makes it difficult to draw reliable conclusions about grouping effects induced by spatial clustering and dot size. Our results provide new insights into biases in numerosity estimation and they demonstrate that the use of LDDs is an effective method to study the human number sense under prolonged viewing.

animal behavior and cognition↗