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Science (New York, N.Y.) Dec 2022Learning to predict rewards based on environmental cues is essential for survival. It is believed that animals learn to predict rewards by updating predictions whenever...
Learning to predict rewards based on environmental cues is essential for survival. It is believed that animals learn to predict rewards by updating predictions whenever the outcome deviates from expectations, and that such reward prediction errors (RPEs) are signaled by the mesolimbic dopamine system-a key controller of learning. However, instead of learning prospective predictions from RPEs, animals can infer predictions by learning the retrospective cause of rewards. Hence, whether mesolimbic dopamine instead conveys a causal associative signal that sometimes resembles RPE remains unknown. We developed an algorithm for retrospective causal learning and found that mesolimbic dopamine release conveys causal associations but not RPE, thereby challenging the dominant theory of reward learning. Our results reshape the conceptual and biological framework for associative learning.
Topics: Animals; Dopamine; Reward; Limbic System; Association Learning; Cues; Mice
PubMed: 36480599
DOI: 10.1126/science.abq6740 -
Science (New York, N.Y.) Oct 2023Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal...
Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal models of the world that enable predictions to be made. The mechanisms that support these associative and predictive aspects of memory are not yet understood. In this study, we used an optogenetic manipulation to perturb the sequential structure, but not global network dynamics, of place cells as rats traversed specific spatial trajectories. This perturbation abolished replay of those trajectories and the development of predictive representations, leading to impaired learning of new optimal trajectories during memory-guided navigation. However, place cell assembly reactivation and reward-context associative learning were unaffected. Our results show a mechanistic dissociation between two complementary hippocampal codes: an associative code (through coactivity) and a predictive code (through sequences).
Topics: Animals; Rats; Conditioning, Classical; Hippocampus; Memory, Episodic; Mental Recall; Optogenetics; Theta Rhythm; Male; Rats, Long-Evans; Association Learning
PubMed: 37856604
DOI: 10.1126/science.adi8237 -
Nature Neuroscience Jan 2020Theories stipulate that memories are encoded within networks of cortical projection neurons. Conversely, GABAergic interneurons are thought to function primarily to...
Theories stipulate that memories are encoded within networks of cortical projection neurons. Conversely, GABAergic interneurons are thought to function primarily to inhibit projection neurons and thereby impose network gain control, an important but purely modulatory role. Here we show in male mice that associative fear learning potentiates synaptic transmission and cue-specific activity of medial prefrontal cortex somatostatin (SST) interneurons and that activation of these cells controls both memory encoding and expression. Furthermore, the synaptic organization of SST and parvalbumin interneurons provides a potential circuit basis for SST interneuron-evoked disinhibition of medial prefrontal cortex output neurons and recruitment of remote brain regions associated with defensive behavior. These data suggest that, rather than constrain mnemonic processing, potentiation of SST interneuron activity represents an important causal mechanism for conditioned fear.
Topics: Animals; Association Learning; Fear; Interneurons; Male; Memory; Mice; Mice, Inbred C57BL; Prefrontal Cortex; Somatostatin; Synaptic Transmission
PubMed: 31844314
DOI: 10.1038/s41593-019-0552-7 -
Nature Reviews. Neuroscience Oct 2019Discoveries over the past two decades demonstrate that regions distributed throughout the association cortex, often called the default network, are suppressed during... (Review)
Review
Discoveries over the past two decades demonstrate that regions distributed throughout the association cortex, often called the default network, are suppressed during tasks that demand external attention and are active during remembering, envisioning the future and making social inferences. This Review describes progress in understanding the organization and function of networks embedded within these association regions. Detailed high-resolution analyses of single individuals suggest that the default network is not a single network, as historically described, but instead comprises multiple interwoven networks. The multiple networks share a common organizational motif (also evident in marmoset and macaque anatomical circuits) that might support a general class of processing function dependent on internally constructed rather than externally constrained representations, with each separate interwoven network specialized for a distinct processing domain. Direct neuronal recordings in humans and monkeys reveal evidence for competitive relationships between the internally and externally oriented networks. Findings from rodent studies suggest that the thalamus might be essential to controlling which networks are engaged through specialized thalamic reticular neurons, including antagonistic subpopulations. These association networks (and presumably thalamocortical circuits) are expanded in humans and might be particularly vulnerable to dysregulation implicated in mental illness.
Topics: Animals; Association Learning; Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Nerve Net
PubMed: 31492945
DOI: 10.1038/s41583-019-0212-7 -
Journal of Psychopharmacology (Oxford,... Apr 2021This paper introduces a new construct, the 'pivotal mental state', which is defined as a hyper-plastic state aiding rapid and deep learning that can mediate... (Review)
Review
This paper introduces a new construct, the 'pivotal mental state', which is defined as a hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation. We believe this new construct bears relevance to a broad range of psychological and psychiatric phenomena. We argue that pivotal mental states serve an important evolutionary function, that is, to aid psychological transformation when actual or perceived environmental pressures demand this. We cite evidence that chronic stress and neurotic traits are primers for a pivotal mental state, whereas acute stress can be a trigger. Inspired by research with serotonin 2A receptor agonist psychedelics, we highlight how activity at this particular receptor can robustly and reliably induce pivotal mental states, but we argue that the capacity for pivotal mental states is an inherent property of the human brain itself. Moreover, we hypothesize that serotonergic psychedelics hijack a system that has evolved to mediate rapid and deep learning when its need is sensed. We cite a breadth of evidences linking stress via a variety of inducers, with an upregulated serotonin 2A receptor system (e.g. upregulated availability of and/or binding to the receptor) and acute stress with 5-HT release, which we argue can activate this primed system to induce a pivotal mental state. The pivotal mental state model is multi-level, linking a specific molecular gateway (increased serotonin 2A receptor signaling) with the inception of a hyper-plastic brain and mind state, enhanced rate of associative learning and the potential mediation of a psychological transformation.
Topics: Aspirations, Psychological; Association Learning; Hallucinogens; Humans; Mindfulness; Mysticism; Neuronal Plasticity; Psychotic Disorders; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Agonists; Signal Transduction; Stress, Physiological; Stress, Psychological
PubMed: 33174492
DOI: 10.1177/0269881120959637 -
Appetite Mar 2020Flavor-consequence learning refers to learned associations between flavor stimuli and post-oral consequences of food that affect food selection, amount eaten and affect.... (Review)
Review
Flavor-consequence learning refers to learned associations between flavor stimuli and post-oral consequences of food that affect food selection, amount eaten and affect. Forms of flavor-consequence learning include flavor aversions, flavor avoidance, conditioned satiety, expected satiety and appetition. Roux-en-Y gastric bypass surgery (RYGB) and other bariatric procedures alter gastrointestinal processing of food in a number of ways. Thus, it is plausible that these procedures alter post-oral unconditioned stimuli that support flavor-consequence learning, leading to altered food selection, amount eaten, and affect. Surprisingly, however, there is almost no research on the role of flavor-consequence learning in the effects of bariatric surgery on appetite. This issue urgently warrants investigation.
Topics: Appetite; Association Learning; Bariatric Surgery; Flavoring Agents; Food Preferences; Gastric Bypass; Humans; Obesity, Morbid; Postoperative Period
PubMed: 31557496
DOI: 10.1016/j.appet.2019.104467 -
Neurobiology of Learning and Memory Jan 2022Although we can learn new information while asleep, we usually cannot consciously remember the sleep-formed memories - presumably because learning occurred in an...
Although we can learn new information while asleep, we usually cannot consciously remember the sleep-formed memories - presumably because learning occurred in an unconscious state. Here, we ask whether sleep-learning expedites the subsequent awake-learning of the same information. To answer this question, we reanalyzed data (Züst et al., 2019, Curr Biol) from napping participants, who learned new semantic associations between pseudowords and translation-words (guga-ship) while in slow-wave sleep. They retrieved sleep-formed associations unconsciously on an implicit memory test following awakening. Then, participants took five runs of paired-associative learning to probe carry-over effects of sleep-learning on awake-learning. Surprisingly, sleep-learning diminished awake-learning when participants learned semantic associations that were congruent to sleep-learned associations (guga-boat). Yet, learning associations that conflicted with sleep-learned associations (guga-coin) was unimpaired relative to learning new associations (resun-table; baseline). We speculate that the impeded wake-learning originated in a deficient synaptic downscaling and resulting synaptic saturation in neurons that were activated during both sleep-learning and awake-learning.
Topics: Adult; Association Learning; Female; Humans; Learning; Male; Mental Recall; Sleep; Vocabulary; Wakefulness; Young Adult
PubMed: 34863922
DOI: 10.1016/j.nlm.2021.107569 -
Science (New York, N.Y.) Nov 2020The sensory neocortex is a critical substrate for memory. Despite its strong connection with the thalamus, the role of direct thalamocortical communication in memory...
The sensory neocortex is a critical substrate for memory. Despite its strong connection with the thalamus, the role of direct thalamocortical communication in memory remains elusive. We performed chronic in vivo two-photon calcium imaging of thalamic synapses in mouse auditory cortex layer 1, a major locus of cortical associations. Combined with optogenetics, viral tracing, whole-cell recording, and computational modeling, we find that the higher-order thalamus is required for associative learning and transmits memory-related information that closely correlates with acquired behavioral relevance. In turn, these signals are tightly and dynamically controlled by local presynaptic inhibition. Our results not only identify the higher-order thalamus as a highly plastic source of cortical top-down information but also reveal a level of computational flexibility in layer 1 that goes far beyond hard-wired connectivity.
Topics: Animals; Association Learning; Auditory Cortex; Memory; Mice; Mice, Inbred C57BL; Neocortex; Neural Pathways; Optogenetics; Patch-Clamp Techniques; Synapses; Thalamus
PubMed: 33184213
DOI: 10.1126/science.abc2399 -
Current Biology : CB Jun 2024Interview with Jingfeng Zhou, who studies how environmental factors impact associative learning and decision-making at the Chinese Institute for Brain Research, Beijing.
Interview with Jingfeng Zhou, who studies how environmental factors impact associative learning and decision-making at the Chinese Institute for Brain Research, Beijing.
Topics: Humans; China; Decision Making; Association Learning; History, 21st Century; Animals
PubMed: 38834018
DOI: 10.1016/j.cub.2024.04.049 -
Behavioural Brain Research Sep 2021Adaptive behaviour is under the potent control of environmental cues. Such cues can acquire value by virtue of their associations with outcomes of motivational... (Review)
Review
Adaptive behaviour is under the potent control of environmental cues. Such cues can acquire value by virtue of their associations with outcomes of motivational significance, be they appetitive or aversive. There are at least two ways through which an environmental cue can acquire value, through first-order and higher-order conditioning. In first-order conditioning, a neutral cue is directly paired with an outcome of motivational significance. In higher-order conditioning, a cue is indirectly associated with motivational events via a directly conditioned first-order stimulus. The present article reviews some of the associations that support learning in first- and higher-order conditioning, as well as the role of the BLA and the molecular mechanisms involved in these two types of learning.
Topics: Animals; Association Learning; Avoidance Learning; Basolateral Nuclear Complex; Behavior, Animal; Cerebral Cortex; Conditioning, Psychological; Motivation
PubMed: 34197867
DOI: 10.1016/j.bbr.2021.113435