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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 -
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 -
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 -
Frontiers in Systems Neuroscience 2020The traditional cerebellum's role has been linked to the high computational demands for sensorimotor control. However, several findings have pointed to its involvement... (Review)
Review
The traditional cerebellum's role has been linked to the high computational demands for sensorimotor control. However, several findings have pointed to its involvement in executive and emotional functions in the last decades. First in 2009 and then, in 2016, we raised why we should consider the cerebellum when thinking about drug addiction. A decade later, mounting evidence strongly suggests the cerebellar involvement in this disorder. Nevertheless, direct evidence is still partial and related mainly to drug-induced reward memory, but recent results about cerebellar functions may provide new insights into its role in addiction. The present review does not intend to be a compelling revision on available findings, as we did in the two previous reviews. This minireview focuses on specific findings of the cerebellum's role in drug-related reward memories and the way ahead for future research. The results discussed here provide grounds for involving the cerebellar cortex's apical region in regulating behavior driven by drug-cue associations. They also suggest that the cerebellar cortex dysfunction may facilitate drug-induced learning by increasing glutamatergic output from the deep cerebellar nucleus (DCN) to the ventral tegmental area (VTA) and neural activity in its projecting areas.
PubMed: 33192350
DOI: 10.3389/fnsys.2020.586574 -
Neuropsychopharmacology : Official... Jan 2016Fear conditioning has been commonly used as a model of emotional learning in animals and, with the introduction of functional neuroimaging techniques, has proven useful... (Review)
Review
Fear conditioning has been commonly used as a model of emotional learning in animals and, with the introduction of functional neuroimaging techniques, has proven useful in establishing the neurocircuitry of emotional learning in humans. Studies of fear acquisition suggest that regions such as amygdala, insula, anterior cingulate cortex, and hippocampus play an important role in acquisition of fear, whereas studies of fear extinction suggest that the amygdala is also crucial for safety learning. Extinction retention testing points to the ventromedial prefrontal cortex as an essential region in the recall of the safety trace, and explicit learning of fear and safety associations recruits additional cortical and subcortical regions. Importantly, many of these findings have implications in our understanding of the pathophysiology of psychiatric disease. Recent studies using clinical populations have lent insight into the changes in regional activity in specific disorders, and treatment studies have shown how pharmaceutical and other therapeutic interventions modulate brain activation during emotional learning. Finally, research investigating individual differences in neurotransmitter receptor genotypes has highlighted the contribution of these systems in fear-associated learning.
Topics: Amygdala; Animals; Association Learning; Brain; Brain Mapping; Extinction, Psychological; Fear; Gyrus Cinguli; Hippocampus; Humans; Nerve Net; Neuroimaging; Panic Disorder; Prefrontal Cortex
PubMed: 26294108
DOI: 10.1038/npp.2015.255 -
Current Opinion in Neurobiology Oct 2018Animals constantly evaluate their environment in order to avoid potential threats and obtain reward in the form of food, shelter and social interactions. In order to... (Review)
Review
Animals constantly evaluate their environment in order to avoid potential threats and obtain reward in the form of food, shelter and social interactions. In order to appropriately respond to sensory cues from the environment, the brain needs to form and store multiple cue-outcome associations. These can then be used to form predictions of the valence of sounds, smells and other sensory inputs arising from the surroundings. However, these associations must be subject to constant update, as the environment can rapidly change. Failing to adapt to such change can be detrimental to survival. Several systems in the mammalian brain have evolved to perform these important behavioral functions. Among these systems, the amygdala and prefrontal cortex are prominent players. Although the amygdala has been shown to form strong cue-outcome associations, the prefrontal cortex is essential for modifying these associations through extinction and reversal learning, and synaptic plasticity occurring in the strong reciprocal connections between these structures is thought to underlie both adaptive and maladaptive learning. Here we review the synaptic organization of the amygdala-prefrontal circuit, and summarize the physiological and behavioral evidence for its involvement in appetitive and aversive learning.
Topics: Amygdala; Animals; Appetitive Behavior; Association; Avoidance Learning; Extinction, Psychological; Humans; Neuronal Plasticity; Prefrontal Cortex; Reversal Learning
PubMed: 29982085
DOI: 10.1016/j.conb.2018.06.006 -
Neuroscience Research Dec 2016Declarative memories are our so-called daily language memories, which we are able to describe or explicitly experience through the act of remembering. This conscious... (Review)
Review
Declarative memories are our so-called daily language memories, which we are able to describe or explicitly experience through the act of remembering. This conscious recollection makes it possible for us to think about the future based on our previous experience (episodic memory) and knowledge (semantic memory). This cognitive function is substantiated by the medial temporal lobe (MTL), a hierarchically organized complex in which the perirhinal cortex and parahippocampal cortex provide item and context information to the hippocampus via the entorhinal cortex, and the hippocampus plays the main role in association and recollection. This conventional view provides an easily understood structure to the declarative memory system. However, neurophysiological studies reporting the activities of single neurons bring a more complicated view. In this article, I review single-unit studies, particularly those focused on the perirhinal cortex and hippocampus, and suggest that association processes for declarative memory are more distributed over the MTL areas. The perirhinal cortex represents both between-domain associations (e.g., item-reward, item-place and item-time) and within-domain associations (e.g., item-item) and contributes to both subcategories of declarative memory (i.e., episodic and semantic memory) in a way that is complementary with the hippocampus.
Topics: Animals; Association; Humans; Memory, Long-Term; Mental Recall; Perirhinal Cortex
PubMed: 27418578
DOI: 10.1016/j.neures.2016.07.001 -
Handbook of Clinical Neurology 2019This chapter presents a summary of current notions regarding cortical specialization for language and a description of the methods employed for the assessment of that... (Review)
Review
This chapter presents a summary of current notions regarding cortical specialization for language and a description of the methods employed for the assessment of that specialization. We distinguish between the "canonical" model of language specialization as it evolved from the early observations of Broca and Wernicke, implicating the inferior frontal gyrus and the posterior temporal cortex of the speech dominant hemisphere (usually the left) and its modern variants that are based on both detailed studies of lesion-symptom correlations and on the results of functional brain mapping methods. The latter fall into two categories. The first includes the invasive ones, namely the Wada procedure for assessing hemispheric dominance for speech and cortical stimulation mapping (whether intraoperative or extraoperative) for identifying cortical nodes or "hubs" of the neuronal network for language. The second category includes the noninvasive methods of functional magnetic resonance imaging, magnetoencephalography, and transcranial magnetic stimulation used for both assessment of hemispheric dominance for language and for localization of the cortical nodes of the language network. The advantages and the shortcomings of all methods are juxtaposed to facilitate selection of particular methods of assessment of the locus of the language network in particular cases.
Topics: Association Learning; Auditory Cortex; Brain Mapping; Cerebral Cortex; Functional Laterality; Humans; Language; Magnetic Resonance Imaging; Transcranial Magnetic Stimulation
PubMed: 31277869
DOI: 10.1016/B978-0-444-64032-1.00031-X -
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 -
Neurobiology of Learning and Memory Sep 2018Many cognitive processes, such as episodic memory and decision making, rely on the ability to form associations between two events that occur separately in time. The... (Review)
Review
Many cognitive processes, such as episodic memory and decision making, rely on the ability to form associations between two events that occur separately in time. The formation of such temporal associations depends on neural representations of three types of information: what has been presented (trace holding), what will follow (temporal expectation), and when the following event will occur (explicit timing). The present review seeks to link these representations with firing patterns of single neurons recorded while rodents and non-human primates associate stimuli, outcomes, and motor responses over time intervals. Across these studies, two distinct firing patterns were observed in the hippocampus, neocortex, and striatum: some neurons change firing rates during or shortly after the stimulus presentation and sustain the firing rate stably or sidlingly during the subsequent intervals (tonic firings). Other neurons transiently change firing rates during a specific moment within the time intervals (phasic firings), and as a group, they form a sequential firing pattern that covers the entire interval. Clever task designs used in some of these studies collectively provide evidence that both tonic and phasic firing responses represent trace holding, temporal expectation, and explicit timing. Subsequently, we applied machine-learning based classification approaches to the two firing patterns within the same dataset collected from rat medial prefrontal cortex during trace eyeblink conditioning. This quantitative analysis revealed that phasic-firing patterns showed greater selectivity for stimulus identity and temporal position than tonic-firing patterns. Our summary illuminates distributed neural representations of temporal association in the forebrain and generates several ideas for future investigations.
Topics: Animals; Association Learning; Behavior, Animal; Brain; Corpus Striatum; Hippocampus; Memory; Neocortex; Neurons; Time Factors
PubMed: 29614377
DOI: 10.1016/j.nlm.2018.03.024