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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 -
Behavioral Neuroscience Apr 2019Occasion setting refers to the ability of 1 stimulus, an occasion setter, to modulate the efficacy of the association between another, conditioned stimulus (CS) and an... (Review)
Review
Occasion setting refers to the ability of 1 stimulus, an occasion setter, to modulate the efficacy of the association between another, conditioned stimulus (CS) and an unconditioned stimulus (US) or reinforcer. Occasion setters and simple CSs are readily distinguished. For example, occasion setters are relatively immune to extinction and counterconditioning, and their combination and transfer functions differ substantially from those of simple CSs. Similarly, the acquisition of occasion setting is favored when stimuli are separated by longer intervals, by empty trace intervals, and are of different modalities, whereas the opposite conditions typically favor the acquisition of simple associations. Furthermore, the simple conditioning and occasion setting properties of a single stimulus can be independent, for example, that stimulus may simultaneously predict the occurrence of a reinforcer and indicate that another stimulus will not be reinforced. Many behavioral phenomena that are intractable to simple associative analysis are better understood within an occasion setting framework. Besides capturing the distinction between direct and modulatory control common to many arenas in neuroscience, occasion setting provides a model for the hierarchical organization of memory for events and event relations, and for contextual control more broadly. Although early lesion studies further differentiated between occasion setting and simple conditioning functions, little is known about the neurobiology of occasion setting. Modern techniques for precise manipulation and monitoring of neuronal activity in multiple brain regions are ideally suited for disentangling contributions of simple conditioning and occasion setting in associative learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Topics: Animals; Association Learning; Basolateral Nuclear Complex; Brain; Conditioning, Psychological; Cues; Discrimination Learning; Extinction, Psychological; Humans; Models, Neurological; Models, Psychological; Motivation; Neural Pathways; Nucleus Accumbens; Prefrontal Cortex; Transfer, Psychology
PubMed: 30907616
DOI: 10.1037/bne0000306 -
Neuron Jun 2011Reward-guided decision-making and learning depends on distributed neural circuits with many components. Here we focus on recent evidence that suggests four frontal lobe... (Review)
Review
Reward-guided decision-making and learning depends on distributed neural circuits with many components. Here we focus on recent evidence that suggests four frontal lobe regions make distinct contributions to reward-guided learning and decision-making: the lateral orbitofrontal cortex, the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex, anterior cingulate cortex, and the anterior lateral prefrontal cortex. We attempt to identify common themes in experiments with human participants and with animal models, which suggest roles that the areas play in learning about reward associations, selecting reward goals, choosing actions to obtain reward, and monitoring the potential value of switching to alternative courses of action.
Topics: Animals; Association Learning; Decision Making; Frontal Lobe; Humans; Neural Pathways; Reward
PubMed: 21689594
DOI: 10.1016/j.neuron.2011.05.014 -
Trends in Neurosciences Mar 2015The study of neurobiological mechanisms underlying anxiety disorders has been shaped by learning models that frame anxiety as maladaptive learning. Pavlovian... (Review)
Review
The study of neurobiological mechanisms underlying anxiety disorders has been shaped by learning models that frame anxiety as maladaptive learning. Pavlovian conditioning and extinction are particularly influential in defining learning stages that can account for symptoms of anxiety disorders. Recently, dynamic and task related communication between the basolateral complex of the amygdala (BLA) and the medial prefrontal cortex (mPFC) has emerged as a crucial aspect of successful evaluation of threat and safety. Ongoing patterns of neural signaling within the mPFC-BLA circuit during encoding, expression and extinction of adaptive learning are reviewed. The mechanisms whereby deficient mPFC-BLA interactions can lead to generalized fear and anxiety are discussed in learned and innate anxiety. Findings with cross-species validity are emphasized.
Topics: Amygdala; Animals; Association Learning; Humans; Mental Recall; Neural Pathways; Prefrontal Cortex
PubMed: 25583269
DOI: 10.1016/j.tins.2014.12.007 -
Neurobiology of Learning and Memory May 2016Underlying many complex behaviors are simple learned associations that allow humans and animals to anticipate the consequences of their actions. The orbitofrontal cortex... (Review)
Review
Underlying many complex behaviors are simple learned associations that allow humans and animals to anticipate the consequences of their actions. The orbitofrontal cortex and basolateral amygdala are two regions which are crucial to this process. In this review, we go back to basics and discuss the literature implicating both these regions in simple paradigms requiring the development of associations between stimuli and the motivationally-significant outcomes they predict. Much of the functional research surrounding this ability has suggested that the orbitofrontal cortex and basolateral amygdala play very similar roles in making these predictions. However, electrophysiological data demonstrates critical differences in the way neurons in these regions respond to predictive cues, revealing a difference in their functional role. On the basis of these data and theories that have come before, we propose that the basolateral amygdala is integral to updating information about cue-outcome contingencies whereas the orbitofrontal cortex is critical to forming a wider network of past and present associations that are called upon by the basolateral amygdala to benefit future learning episodes. The tendency for orbitofrontal neurons to encode past and present contingencies in distinct neuronal populations may facilitate its role in the formation of complex, high-dimensional state-specific associations.
Topics: Animals; Association Learning; Basolateral Nuclear Complex; Humans; Prefrontal Cortex
PubMed: 27112314
DOI: 10.1016/j.nlm.2016.04.009 -
Neurobiology of Learning and Memory Mar 2020In rodents, the anterior cingulate (ACC), prelimbic (PL), and infralimbic cortex (IL) comprise the medial prefrontal cortex (mPFC). Through extensive connections with... (Review)
Review
In rodents, the anterior cingulate (ACC), prelimbic (PL), and infralimbic cortex (IL) comprise the medial prefrontal cortex (mPFC). Through extensive connections with cortical and subcortical structures, the mPFC plays a key modulatory role in the neuronal circuits underlying associative fear and reward learning. In this article, we have compiled the evidence that associative learning induces plasticity in both the intrinsic and synaptic excitability of mPFC neurons to modulate conditioned fear and cocaine seeking behavior. The literature highlights the accumulating evidence that plasticity in the intrinsic excitability of mPFC neurons represents a major cellular mechanism that interacts with synaptic changes to alter the impact of the mPFC on fear and reward circuits.
Topics: Action Potentials; Animals; Association Learning; Conditioning, Classical; Drug-Seeking Behavior; Extinction, Psychological; Fear; Humans; Neuronal Plasticity; Neurons; Prefrontal Cortex; Reward
PubMed: 31765801
DOI: 10.1016/j.nlm.2019.107117 -
NeuroImage Apr 2020Creative thinking relies on the ability to make remote associations and fruitfully combine unrelated concepts. Hence, original associations and bi-associations (i.e.,...
Creative thinking relies on the ability to make remote associations and fruitfully combine unrelated concepts. Hence, original associations and bi-associations (i.e., associations to one and two concepts, respectively) are considered elementary cognitive processes of creative cognition. In this work, we investigated the cognitive and brain mechanisms underlying these association processes with tasks that asked for original associations to either one or two adjective stimuli. Study 1 showed that the generation of more original associations and bi-associations was related to several indicators of creativity, corroborating the validity of these association performances as basic processes underlying creative cognition. Study 2 assessed brain activity during performance of these association tasks by means of fMRI. The generation of original versus common associations was related to higher activation in bilateral lingual gyri suggesting that cued search for remote representatives of given properties are supported by visually-mediated search strategies. Parametric analyses further showed that the generation of more original associations involved activation of the left inferior frontal cortex and the left ventromedial prefrontal cortex, which are consistently implicated in constrained retrieval and evaluation processes, and relevant for making distant semantic connections. Finally, the generation of original bi-associations involved higher activation in bilateral hippocampus and inferior parietal lobe, indicating that conceptual combination recruits episodic simulation processes. Together, these findings suggest that the generation of verbally cued, original associations relies not only on verbal semantic memory but involves mental imagery and episodic simulation, offering new insights in the nuanced interplay of memory systems in creative thought.
Topics: Adolescent; Adult; Association; Brain Mapping; Cerebral Cortex; Creativity; Cues; Female; Hippocampus; Humans; Imagination; Language; Magnetic Resonance Imaging; Male; Memory, Episodic; Young Adult
PubMed: 32001370
DOI: 10.1016/j.neuroimage.2020.116586 -
PloS One 2014The basic structure of the cortico-hippocampal system is highly conserved across mammalian species. Comparatively few hippocampal neurons can represent and address a...
The basic structure of the cortico-hippocampal system is highly conserved across mammalian species. Comparatively few hippocampal neurons can represent and address a multitude of cortical patterns, establish associations between cortical patterns and consolidate these associations in the cortex. In this study, we investigate how elementary anatomical properties in the cortex-hippocampus loop along with synaptic plasticity contribute to these functions. Specifically, we focus on the high degree of connectivity between cortex and hippocampus leading to converging and diverging forward and backward projections and heterogenous synaptic transmission delays that result from the detached location of the hippocampus and its multiple loops. We found that in a model incorporating these concepts, each cortical pattern can evoke a unique spatio-temporal spiking pattern in hippocampal neurons. This hippocampal response facilitates a reliable disambiguation of learned associations and a bridging of a time interval larger than the time window of spike-timing dependent plasticity in the cortex. Moreover, we found that repeated retrieval of a stored association leads to a compression of the interval between cue presentation and retrieval of the associated pattern from the cortex. Neither a high degree of connectivity nor heterogenous synaptic delays alone is sufficient for this behavior. We conclude that basic anatomical properties between cortex and hippocampus implement mechanisms for representing and consolidating temporal information. Since our model reveals the observed functions for a range of parameters, we suggest that these functions are robust to evolutionary changes consistent with the preserved function of the hippocampal loop across different species.
Topics: Algorithms; Animals; Association Learning; Cerebral Cortex; Hippocampus; Humans; Models, Neurological; Neural Pathways; Neuronal Plasticity; Neurons
PubMed: 24404200
DOI: 10.1371/journal.pone.0085016 -
Neuron Oct 2020The representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed...
The representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed 2-photon imaging to examine the representation of odors in piriform and in two downstream areas, the orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC), as mice learned olfactory associations. In piriform, we observed that odor responses were largely unchanged during learning. In OFC, 30% of the neurons acquired robust responses to conditioned stimuli (CS+) after learning, and these responses were gated by internal state and task context. Moreover, direct projections from piriform to OFC can be entrained to elicit learned olfactory behavior. CS+ responses in OFC diminished with continued training, whereas persistent representations of both CS+ and CS- odors emerged in mPFC. Optogenetic silencing indicates that these two brain structures function sequentially to consolidate the learning of appetitive associations.
Topics: Animals; Appetitive Behavior; Association Learning; Conditioning, Classical; Intravital Microscopy; Mice; Microscopy, Fluorescence, Multiphoton; Neurons; Odorants; Olfactory Pathways; Optogenetics; Piriform Cortex; Prefrontal Cortex
PubMed: 32827456
DOI: 10.1016/j.neuron.2020.07.033 -
The Journal of Neuroscience : the... Aug 2018Behavioral evidence suggests that beliefs about causal structure constrain associative learning, determining which stimuli can enter into association, as well as the... (Comparative Study)
Comparative Study
Behavioral evidence suggests that beliefs about causal structure constrain associative learning, determining which stimuli can enter into association, as well as the functional form of that association. Bayesian learning theory provides one mechanism by which structural beliefs can be acquired from experience, but the neural basis of this mechanism is poorly understood. We studied this question with a combination of behavioral, computational, and neuroimaging techniques. Male and female human subjects learned to predict an outcome based on cue and context stimuli while being scanned using fMRI. Using a model-based analysis of the fMRI data, we show that structure learning signals are encoded in posterior parietal cortex, lateral prefrontal cortex, and the frontal pole. These structure learning signals are distinct from associative learning signals. Moreover, representational similarity analysis and information mapping revealed that the multivariate patterns of activity in posterior parietal cortex and anterior insula encode the full posterior distribution over causal structures. Variability in the encoding of the posterior across subjects predicted variability in their subsequent behavioral performance. These results provide evidence for a neural architecture in which structure learning guides the formation of associations. Animals are able to infer the hidden structure behind causal relations between stimuli in the environment, allowing them to generalize this knowledge to stimuli they have never experienced before. A recently published computational model based on this idea provided a parsimonious account of a wide range of phenomena reported in the animal learning literature, suggesting a dedicated neural mechanism for learning this hidden structure. Here, we validate this model by measuring brain activity during a task that involves both structure learning and associative learning. We show that a distinct network of regions supports structure learning and that the neural signal corresponding to beliefs about structure predicts future behavioral performance.
Topics: Anticipation, Psychological; Association Learning; Bayes Theorem; Brain Mapping; Causality; Cues; Female; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Models, Neurological; Models, Psychological; Parietal Lobe; Prefrontal Cortex
PubMed: 29959234
DOI: 10.1523/JNEUROSCI.3336-17.2018