The Neuroscience of Mammalian Associative Learning

Department of Psychology and Brain Research Institute, University of California-Los Angeles, Los Angeles, CA 90095-1563, USA.
Annual Review of Psychology (Impact Factor: 21.81). 02/2005; 56(1):207-34. DOI: 10.1146/annurev.psych.56.091103.070213
Source: PubMed


Mammalian associative learning is organized into separate anatomically defined functional systems. We illustrate the organization of two of these systems, Pavlovian fear conditioning and Pavlovian eyeblink conditioning, by describing studies using mutant mice, brain stimulation and recording, brain lesions and direct pharmacological manipulations of specific brain regions. The amygdala serves as the neuroanatomical hub of the former, whereas the cerebellum is the hub of the latter. Pathways that carry information about signals for biologically important events arrive at these hubs by circuitry that depends on stimulus modality and complexity. Within the amygdala and cerebellum, neural plasticity occurs because of convergence of these stimuli and the biologically important information they predict. This neural plasticity is the physical basis of associative memory formation, and although the intracellular mechanisms of plasticity within these structures share some similarities, they differ significantly. The last Annual Review of Psychology article to specifically tackle the question of mammalian associative learning ( Lavond et al. 1993 ) persuasively argued that identifiable "essential" circuits encode memories formed during associative learning. The next dozen years saw breathtaking progress not only in detailing those essential circuits but also in identifying the essential processes occurring at the synapses (e.g., Bi & Poo 2001, Martinez & Derrick 1996 ) and within the neurons (e.g., Malinow & Malenka 2002, Murthy & De Camilli 2003 ) that make up those circuits. In this chapter, we describe the orientation that the neuroscience of learning has taken and review some of the progress made within that orientation.

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    • "Pavlovian conditioned stimuli (CS; e.g., tone) produce defensive behaviors such as freezing after being paired with an aversive unconditioned stimulus (US; e.g., footshock; Pavlov, 1927). This form of learning depends on neural connections in the amygdala (LeDoux, 2000; Goosens and Maren, 2001; Fanselow and Poulos, 2005; Maren, 2005; Herry and Johansen, 2014; Lüthi and Lüscher, 2014; Janak and Tye, 2015). While the term Pavlovian fear conditioning is commonly used to describe this procedure, it implies that the subjective mental state of fear is being acquired. "
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    ABSTRACT: Two studies explored the role of the amygdala in response modulation by an aversive conditioned stimulus (CS) in rats. Experiment 1 investigated the role of amygdala circuitry in conditioned suppression using a paradigm in which licking for sucrose was inhibited by a tone CS that had been previously paired with footshock. Electrolytic lesions of the lateral amygdala (LA) impaired suppression relative to sham-operated animals, and produced the same pattern of results when applied to central amygdala. In addition, disconnection of the lateral and central amygdala, by unilateral lesion of each on opposite sides of the brain, also impaired suppression relative to control subjects that received lesions of both areas on the same side. In each case, lesions were placed following Pavlovian conditioning and instrumental training, but before testing. This procedure produced within-subjects measures of the effects of lesion on freezing and between-group comparisons for the effects on suppression. Experiment 2 extended this analysis to a task where an aversive CS suppressed shuttling responses that had been previously food reinforced and also found effects of bilateral lesions of the central amygdala in a pre-post design. Together, these studies demonstrate that connections between the lateral and central amygdala constitute a serial circuit involved in processing aversive Pavlovian stimuli, and add to a growing body of findings implicating central amygdala in the modulation of instrumental behavior.
    Frontiers in Behavioral Neuroscience 11/2015; 9. DOI:10.3389/fnbeh.2015.00293 · 3.27 Impact Factor
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    • "In term of the cellular mechanisms for associative memory, activity-dependent plasticity at the synapses and neurons, e.g., long-term Abbreviations: CR, conditioning response and conditioned reflex; WS, whisker stimulus; OS, odor stimulus; LFP, local field potential; PSG, paired stimulus group; UPSG, unpaired stimulus group, NCG, naïve control group. potentiation and depression, is presumably involved (Aou et al., 1992; Bliss and Collingridge, 1993; Alkon, 1998; Honey and Good, 2000; Blair et al., 2001; Christian and Thompson, 2003; Jones et al., 2003; Silva, 2003; Roman et al., 2004; Zhang et al., 2004; Dityatev and Bolshakov, 2005; Fanselow and Poulos, 2005; Weeks et al., 2007; Frey and Frey, 2008; Mozzachiodi et al., 2008; Neves et al., 2008; Nikitin et al., 2008; Sah et al., 2008; Wesson et al., 2008; Pape and Pare, 2010; Rosselet et al., 2011). Experience-dependent learning led to structural plasticity in spines and excitatory synapses (Trachtenberg et al., 2002; Sadaka et al., 2003; Holtmaat and Svoboda, 2009; Mégevand et al., 2009; Harlow et al., 2010; Wilbrecht et al., 2010; Ashby and Isaac, 2011; Cheetham et al., 2012; Margolis et al., 2012). "
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    ABSTRACT: Associative learning and memory are essential to logical thinking and cognition. How the neurons are recruited as associative memory cells to encode multiple input signals for their associated storage and distinguishable retrieval remains unclear. We studied this issue in the barrel cortex by in vivo two-photon calcium imaging, electrophysiology, and neural tracing in our mouse model that the simultaneous whisker and olfaction stimulations led to odorant-induced whisker motion. After this cross-modal reflex arose, the barrel and piriform cortices connected. More than 40% of barrel cortical neurons became to encode odor signal alongside whisker signal. Some of these neurons expressed distinct activity patterns in response to acquired odor signal and innate whisker signal, and others encoded similar pattern in response to these signals. In the meantime, certain barrel cortical astrocytes encoded odorant and whisker signals. After associative learning, the neurons and astrocytes in the sensory cortices are able to store the newly learnt signal (cross-modal memory) besides the innate signal (native-modal memory). Such associative memory cells distinguish the differences of these signals by programming different codes and signify the historical associations of these signals by similar codes in information retrievals.
    Frontiers in Cellular Neuroscience 08/2015; 9(320):1-17. DOI:10.3389/fncel.2015.00320 · 4.29 Impact Factor
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    • "Learning to avoid physically harmful situations is critical for the survival of organisms. Aversive learning is formed when a certain neutral situation (conditioned stimulus or CS) is associated with the physically harmful situation (unconditioned stimulus or US) (Fanselow and Poulos, 2005; LeDoux, 2000). In rodents, fear (which does not mean the conscious feeling of fear, but instead, a defensive response to a threat) manifests as immobility or ''freezing'' under environmental conditions that predict pain—the major sensory modality of the physical harm (Herry and Johansen, 2014; Pape and Pare, 2010). "
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    ABSTRACT: Animals learn to avoid harmful situations by associating a neutral stimulus with a painful one, resulting in a stable threat memory. In mammals, this form of learning requires the amygdala. Although pain is the main driver of aversive learning, the mechanism that transmits pain signals to the amygdala is not well resolved. Here, we show that neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus are critical for relaying pain signals to the central nucleus of amygdala and that this pathway may transduce the affective motivational aspects of pain. Genetic silencing of CGRP neurons blocks pain responses and memory formation, whereas their optogenetic stimulation produces defensive responses and a threat memory. The pain-recipient neurons in the central amygdala expressing CGRP receptors are also critical for establishing a threat memory. The identification of the neural circuit conveying affective pain signals may be pertinent for treating pain conditions with psychiatric comorbidities. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 07/2015; 162(2):363. DOI:10.1016/j.cell.2015.05.057 · 32.24 Impact Factor
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