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Learning & Memory (Cold Spring Harbor,... 2003This study reviews the role of the serotonin 5-HT2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane... (Review)
Review
This study reviews the role of the serotonin 5-HT2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as BOL (d-bromolysergic acid diethylamide), LY53,857, and ketanserin acted as neutral antagonists in that they had no effect on learning, whereas others (MDL11,939, ritanserin, and mianserin) acted as inverse agonists in that they retarded learning through an action at the 5-HT2A receptor. These results were placed in the context of what is known concerning the anatomical distribution and electrophysiological effects of 5-HT2A receptor activation in frontal cortex and hippocampus, as well as the role of cortical 5-HT2A receptors in schizophrenia. It was concluded that the 5-HT2A receptor demonstrates constitutive activity, and that variations in this activity can produce profound alterations in cognitive states.
Topics: Animals; Association Learning; Brain; Cognition; Conditioning, Classical; Ergolines; Frontal Lobe; Hallucinogens; Hippocampus; Ketanserin; Lysergic Acid Diethylamide; Mianserin; Nictitating Membrane; Piperidines; Rabbits; Receptor, Serotonin, 5-HT2A; Ritanserin; Schizophrenia; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Serotonin Receptor Agonists
PubMed: 14557608
DOI: 10.1101/lm.60803 -
The Journal of Neuroscience : the... Feb 2022Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral...
Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the activity of the LEC for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the efferent targets of the LEC, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer's disease. To recall past events, the brain needs to reactivate the activity patterns that occurred during those events. However, such reinstatement of memory traces is not trivial because it goes against the natural tendency of the brain to restructure the activity patterns continuously. We found that dysfunction of a brain region called the LEC worsened the drift of the brain activity when rats repeatedly underwent the same events in the same room and made them behave as if they had never experienced these events before. Thus, the LEC stabilizes the brain activity to facilitate the recovery of the original memory trace. Failure of this process might underlie memory problems in elderly and Alzheimer's disease patients with the degenerated LEC.
Topics: Animals; Association Learning; Entorhinal Cortex; Male; Mental Recall; Neurons; Rats; Rats, Long-Evans
PubMed: 34911795
DOI: 10.1523/JNEUROSCI.1439-21.2021 -
The Journal of Neuroscience : the... May 2022Although the cerebellum has been traditionally considered to be exclusively involved in motor control, recent anatomic and clinical studies show that it also has a role...
Although the cerebellum has been traditionally considered to be exclusively involved in motor control, recent anatomic and clinical studies show that it also has a role in reward-processing. However, the way in which the movement-related and the reward-related neural activity interact at the level of the cerebellar cortex and contribute toward learning is still unclear. Here, we studied the simple spike activity of Purkinje cells in the mid-lateral cerebellum when 2 male monkeys learned to associate a right or left-hand movement with one of two visual symbolic cues. These cells had distinctly different discharge patterns between an overtrained symbol-hand association and a novel symbol-hand association, responding in association with the movement of both hands, although the kinematics of the movement did not change between the two conditions. The activity change was not related to the pattern of the visual symbols, the movement kinematics, the monkeys' reaction times, or the novelty of the visual symbols. The simple spike activity changed throughout the learning process, but the concurrent complex spikes did not instruct that change. Although these neurons also have reward-related activity, the reward-related and movement-related signals were independent. We suggest that this mixed selectivity may facilitate the flexible learning of difficult reinforcement learning problems. The cerebellum receives both motor-related and reward-related information. However, it is unclear how these two signals interact at the level of cerebellar cortex and contribute to learning nonmotor skills. Here we show that in the mid-lateral cerebellum, the reward information is encoded independently from the motor information such that during reward-based learning, only the reward information carried by the Purkinje cells inform learning while the motor information remains unchanged with learning.
Topics: Animals; Association Learning; Cerebellum; Female; Haplorhini; Learning; Male; Movement; Purkinje Cells; Reward
PubMed: 35351828
DOI: 10.1523/JNEUROSCI.1771-21.2022 -
Neuroscience and Biobehavioral Reviews Jan 2020The ability to pick out a unique entity with a proper name is an important component of human language. It has been a primary focus of research in the philosophy of... (Review)
Review
The ability to pick out a unique entity with a proper name is an important component of human language. It has been a primary focus of research in the philosophy of language since the nineteenth century. Brain-based evidence has shed new light on this capacity, and an extensive literature indicates the involvement of distinct fronto-temporal and temporo-occipito-parietal association cortices in proper-name retrieval. However, comparatively few efforts have sought to explain how memory encoding processes lead to the later recruitment of these distinct regions at retrieval. Here, we provide a unified account of proper-name encoding and retrieval, reviewing evidence that socio-emotional and unitized encoding subserve the retrieval of proper names via anterior-temporal-prefrontal activations. Meanwhile, non-unitized item-item and item-context encoding support subsequent retrieval, largely dependent on the temporo-occipito-parietal cortex. We contend that this well-established divergence in encoding systems can explain how proper names are later retrieved from distinct neural structures. Furthermore, we explore how evidence reviewed here can inform a century-and-a-half-old debate about proper names and the meanings they pick out.
Topics: Association; Cerebral Cortex; Humans; Mental Recall; Names; Recognition, Psychology
PubMed: 31734171
DOI: 10.1016/j.neubiorev.2019.11.005 -
The Journal of Neuroscience : the... Dec 2021Learned associations between stimuli allow us to model the world and make predictions, crucial for efficient behavior (e.g., hearing a siren, we expect to see an...
Learned associations between stimuli allow us to model the world and make predictions, crucial for efficient behavior (e.g., hearing a siren, we expect to see an ambulance and quickly make way). While there are theoretical and computational frameworks for prediction, the circuit and receptor-level mechanisms are unclear. Using high-density EEG, Bayesian modeling, and machine learning, we show that inferred "causal" relationships between stimuli and frontal alpha activity account for reaction times (a proxy for predictions) on a trial-by-trial basis in an audiovisual delayed match-to-sample task which elicited predictions. Predictive β feedback activated sensory representations in advance of predicted stimuli. Low-dose ketamine, an NMDAR blocker, but not the control drug dexmedetomidine, perturbed behavioral indices of predictions, their representation in higher-order cortex, feedback to posterior cortex, and pre-activation of sensory templates in higher-order sensory cortex. This study suggests that predictions depend on alpha activity in higher-order cortex, β feedback, and NMDARs, and ketamine blocks access to learned predictive information. We learn the statistical regularities around us, creating associations between sensory stimuli. These associations can be exploited by generating predictions, which enable fast and efficient behavior. When predictions are perturbed, it can negatively influence perception and even contribute to psychiatric disorders, such as schizophrenia. Here we show that the frontal lobe generates predictions and sends them to posterior brain areas, to activate representations of predicted sensory stimuli before their appearance. Oscillations in neural activity (α and β waves) are vital for these predictive mechanisms. The drug ketamine blocks predictions and the underlying mechanisms. This suggests that the generation of predictions in the frontal lobe, and the feedback pre-activating sensory representations in advance of stimuli, depend on NMDARs.
Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Association Learning; Brain; Dexmedetomidine; Excitatory Amino Acid Antagonists; Feedback; Female; Humans; Ketamine; Male; Reaction Time; Receptors, N-Methyl-D-Aspartate
PubMed: 34732525
DOI: 10.1523/JNEUROSCI.1311-21.2021 -
The International Journal of... Feb 2013Like other physiological responses, immune functions are the subject of behavioural conditioning. Conditioned immunosuppression can be induced by contingently pairing a...
Like other physiological responses, immune functions are the subject of behavioural conditioning. Conditioned immunosuppression can be induced by contingently pairing a novel taste with an injection of the immunosuppressant cyclosporine A (CsA) in an associative learning paradigm. This learned immunosuppression is centrally mediated by the insular cortex and the amygdala. However, the afferent mechanisms by which the brain detects CsA are not understood. In this study we analysed whether CsA is sensed via the chemosensitive vagus nerve or whether CsA directly acts on the brain. Our experiments revealed that a single peripheral administration of CsA increases neuronal activity in the insular cortex and the amygdala as evident from increased electric activity, c-Fos expression and amygdaloid noradrenaline release. However, this increased neuronal activity was not affected by prior vagal deafferentation but rather seems to partially be induced by direct action of CsA on cortico-amygdaloid structures and the chemosensitive brainstem regions area postrema and nucleus of the solitary tract. Together, these data indicate that CsA as an unconditioned stimulus may directly act on the brain by a still unknown transduction mechanism.
Topics: Amygdala; Animals; Association Learning; Cerebral Cortex; Cyclosporine; Immunosuppression Therapy; Male; Rats; Vagus Nerve
PubMed: 22217400
DOI: 10.1017/S1461145711001799 -
The Journal of Neuroscience : the... Aug 2017It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in...
It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword-object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for experimental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary. Learning a task involves the brain system within which that specific task becomes established. Therefore, successfully learning a new vocabulary establishes the novel words in the language system. However, there is evidence that in the early stages of learning, networks within multiple-demand cortex (MDC), which control higher cognitive functions, such as working memory, attention, and monitoring of performance, become active. This activity declines once the task is learnt. The present study demonstrated that a node within MDC, located in midline frontal cortex, becomes active during the early stage of learning a novel vocabulary. Importantly, noninvasive brain stimulation of this node improved performance during this stage of learning. This observation demonstrated that MDC activity is important for learning.
Topics: Acoustic Stimulation; Adult; Aged; Association Learning; Cerebral Cortex; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Photic Stimulation; Random Allocation; Reaction Time; Transcranial Magnetic Stimulation; Verbal Learning; Vocabulary; Young Adult
PubMed: 28676576
DOI: 10.1523/JNEUROSCI.3857-16.2017 -
Neurobiology of Learning and Memory Oct 2015While contemporary neuroscience is paying increasing attention to subcellular and molecular events and other intracellular phenomena underlying the acquisition, storage,... (Review)
Review
Functional basis of associative learning and its relationships with long-term potentiation evoked in the involved neural circuits: Lessons from studies in behaving mammals.
While contemporary neuroscience is paying increasing attention to subcellular and molecular events and other intracellular phenomena underlying the acquisition, storage, and retrieval of newly acquired motor and cognitive abilities, parallel attention should be paid to the study of the electrophysiological phenomena taking place at selected cortical and subcortical neuronal and synaptic sites during the precise moment of learning acquisition, extinction, and recall. These in vivo approaches to the study of learning and memory processes will allow the proper integration of the important information collected from in vitro and delayed molecular studies. Here, we summarize studies in behaving mammals carried out in our laboratory during the past ten years on the relationships between experimentally evoked long-term potentiation (LTP) and activity-dependent changes in synaptic strength taking place in hippocampal, prefrontal and related cortical and subcortical circuits during the acquisition of classical eyeblink conditioning or operant learning tasks. These studies suggest that different hippocampal synapses are selectively modified in strength during the acquisition of classical, but not instrumental, learning tasks. In contrast, selected prefrontal and striatum synapses are more directly modified by operant conditioning. These studies also show that besides N-methyl-D-aspartate (NMDA) receptors, many other neurotransmitter, intracellular mediating, and transcription factors participate in these two types of associative learning. Although experimentally evoked LTP seems to prevent the acquisition of classical eyeblink conditioning when induced at selected hippocampal synapses, it proved to be ineffective in preventing the acquisition of operant conditioned tasks when induced at numerous hippocampal, prefrontal, and striatal sites. The differential roles of these cortical structures during these two types of associative learning are discussed, and a diagrammatic representation of their respective functions is presented.
Topics: Animals; Association Learning; Behavior, Animal; Brain; Cognition; Conditioning, Classical; Conditioning, Eyelid; Conditioning, Operant; Hippocampus; Long-Term Potentiation; Neurons; Prefrontal Cortex; Synapses
PubMed: 25916668
DOI: 10.1016/j.nlm.2015.04.006 -
Nature Communications Mar 2019Animals rely on learned associations to make decisions. Associations can be based on relationships between object features (e.g., the three leaflets of poison ivy...
Animals rely on learned associations to make decisions. Associations can be based on relationships between object features (e.g., the three leaflets of poison ivy leaves) and outcomes (e.g., rash). More often, outcomes are linked to multidimensional states (e.g., poison ivy is green in summer but red in spring). Feature-based reinforcement learning fails when the values of individual features depend on the other features present. One solution is to assign value to multi-featural conjunctive representations. Here, we test if the hippocampus forms separable conjunctive representations that enables the learning of response contingencies for stimuli of the form: AB+, B-, AC-, C+. Pattern analyses on functional MRI data show the hippocampus forms conjunctive representations that are dissociable from feature components and that these representations, along with those of cortex, influence striatal prediction errors. Our results establish a novel role for hippocampal pattern separation and conjunctive representation in reinforcement learning.
Topics: Adult; Association Learning; Brain Mapping; Conditioning, Classical; Corpus Striatum; Female; Hippocampus; Humans; Linear Models; Magnetic Resonance Imaging; Male; Models, Neurological; Reinforcement, Psychology; Young Adult
PubMed: 30842581
DOI: 10.1038/s41467-019-08998-1 -
Acta Neurobiologiae Experimentalis 1988Organization of intrinsic connections of the frontal association cortex (FAC) in dogs was studied using retrograde HRP-transport method. For cytoarchitectonic...
Organization of intrinsic connections of the frontal association cortex (FAC) in dogs was studied using retrograde HRP-transport method. For cytoarchitectonic observations and measurements of thickness of the cortex and its particular layers, additional sections stained with Nissl method were examined. Organization of intrinsic connections showed that within the dog's FAC two main cortical zones could be distinguished - the dorsal and the ventral one. The dorsal zone involves dorsally situated areas on the lateral and medial aspects of the hemisphere, which belong to the prefrontal and premotor regions. The vientral zone consists only of prefrontal areas situated ventrally on both aspects of the hemisphere. Each of the zones is characterized by strong mutual intrinsic connections and weak connections with the other zone. At the border there is a transitional area in which connections from both dorsal and ventral zones overlap. The cytoarchitectonic observations indicated that the dorsal and ventral zones can be distinguished in the central and caudal, but not in the rostral FAC subregion. The dorsal zone is characterized by considerable thickness of the cortex, cortical layers III and V, and the presence in these layers of scattered, large pyramidal neurons. The ventral zone has thinner cortex and layers III and V, and their pyramidal neurons are more uniform in size. In none of the zones clearly defined granular layer IV was observed.
Topics: Animals; Association; Brain Mapping; Dogs; Frontal Lobe; Horseradish Peroxidase
PubMed: 3188998
DOI: No ID Found