Normal Aging Alters Learning and Attention-Related Teaching Signals in Basolateral Amygdala

Normal aging has been associated with an increased propensity to wait for rewards. When this is tested experimentally, rewards are typically offered at increasing delays. In this setting, persistent responding for delayed rewards in aged rats could reflect either changes in the evaluation of delayed rewards or diminished learning, perhaps due to the loss of subcortical teaching signals induced by changes in reward; the loss or diminution of such teaching signals would result in slower learning with progressive delay of reward, which would appear as persistent responding. Such teaching signals have commonly been reported in phasic firing of midbrain dopamine neurons; however, similar signals have also been found in reward-responsive neurons in the basolateral amygdala (ABL). Unlike dopaminergic teaching signals, those in ABL seem to reflect surprise, increasing when reward is either better or worse than expected. Accordingly, activity is correlated with attentional responses and with the speed of learning after surprising increases or decreases in reward. Here we examined whether these attention-related teaching signals might be altered in normal aging. Young (3–6 months) and aged (22–26 months) male Long–Evans rats were trained on a discounting task used previously to demonstrate these signals. As expected, aged rats were less sensitive to delays, and this change was associated with a loss of attentional changes in orienting behavior and neural activity. These results indicate that normal aging alters teaching signals in the ABL. Changes in these teaching signals may contribute to a host of age-related cognitive changes.

[1]  B. Richmond,et al.  Neuronal Signals in the Monkey Basolateral Amygdala during Reward Schedules , 2005, The Journal of Neuroscience.

[2]  Aging Neuroscience , 2022 .

[3]  A. Logue,et al.  Adjusting delay to reinforcement: comparing choice in pigeons and humans. , 1988, Journal of experimental psychology. Animal behavior processes.

[4]  H. de Wit,et al.  Determination of discount functions in rats with an adjusting-amount procedure. , 1997, Journal of the experimental analysis of behavior.

[5]  N. Petry Pathological gamblers, with and without substance use disorders, discount delayed rewards at high rates. , 2001, Journal of abnormal psychology.

[6]  Daeyeol Lee,et al.  Neuronal basis of age-related working memory decline , 2011, Nature.

[7]  Elizabeth A. West,et al.  Transient Inactivation of Orbitofrontal Cortex Blocks Reinforcer Devaluation in Macaques , 2011, The Journal of Neuroscience.

[8]  J. Pearce,et al.  The Influence of Predictive Accuracy on Serial Conditioning in the Rat , 1988 .

[9]  Susan M Resnick,et al.  Age differences in orbitofrontal activation: an fMRI investigation of delayed match and nonmatch to sample , 2004, NeuroImage.

[10]  G. Schoenbaum,et al.  Orbitofrontal Cortex and Representation of Incentive Value in Associative Learning , 1999, The Journal of Neuroscience.

[11]  J. O'Doherty,et al.  Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex , 2003, Science.

[12]  N. Daw,et al.  Differential roles of human striatum and amygdala in associative learning , 2011, Nature Neuroscience.

[13]  A. Tversky,et al.  Choices, Values, and Frames , 2000 .

[14]  H Nishijo,et al.  Single neuron responses in amygdala of alert monkey during complex sensory stimulation with affective significance , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  G. Schoenbaum,et al.  Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning , 1998, Nature Neuroscience.

[16]  Guillem R. Esber,et al.  Neural Correlates of Variations in Event Processing during Learning in Basolateral Amygdala , 2010, The Journal of Neuroscience.

[17]  Morgan D. Barense,et al.  Aged rats are impaired on an attentional set-shifting task sensitive to medial frontal cortex damage in young rats. , 2002, Learning & memory.

[18]  J. Elster,et al.  Choice Over Time , 1992 .

[19]  N. Petry,et al.  Delay discounting of money and alcohol in actively using alcoholics, currently abstinent alcoholics, and controls , 2001, Psychopharmacology.

[20]  Joseph J. Paton,et al.  Expectation Modulates Neural Responses to Pleasant and Aversive Stimuli in Primate Amygdala , 2007, Neuron.

[21]  Paul E. Gilbert,et al.  A comparison of discrimination and reversal learning for olfactory and visual stimuli in aged rats. , 2008, Behavioral neuroscience.

[22]  Geoffrey Schoenbaum,et al.  Teaching old rats new tricks: age-related impairments in olfactory reversal learning , 2002, Neurobiology of Aging.

[23]  Domenic H. Cerri,et al.  Willingness to Wait and Altered Encoding of Time-Discounted Reward in the Orbitofrontal Cortex with Normal Aging , 2012, The Journal of Neuroscience.

[24]  M. Roesch,et al.  Dopamine neurons encode the better option in rats deciding between differently delayed or sized rewards , 2007, Nature Neuroscience.

[25]  M. Walton,et al.  Separate neural pathways process different decision costs , 2006, Nature Neuroscience.

[26]  E. Murray,et al.  Bilateral Orbital Prefrontal Cortex Lesions in Rhesus Monkeys Disrupt Choices Guided by Both Reward Value and Reward Contingency , 2004, The Journal of Neuroscience.

[27]  S. Mobini,et al.  Theory and method in the quantitative analysis of ”impulsive choice” behaviour: implications for psychopharmacology , 1999, Psychopharmacology.

[28]  H Rachlin,et al.  Commitment, choice and self-control. , 1972, Journal of the experimental analysis of behavior.

[29]  Susan M Resnick,et al.  Aging and prefrontal functions: dissociating orbitofrontal and dorsolateral abilities , 2004, Neurobiology of Aging.

[30]  B. Setlow,et al.  Good things come to those who wait: Attenuated discounting of delayed rewards in aged Fischer 344 rats , 2010, Neurobiology of Aging.

[31]  M. Dixon,et al.  Delay discounting by pathological gamblers. , 2003, Journal of applied behavior analysis.

[32]  Robert C. Wilson,et al.  Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex , 2011, Nature Neuroscience.

[33]  Paola Manzini,et al.  Choice Over Time , 2007, The Handbook of Rational and Social Choice.

[34]  M. D’Esposito,et al.  Isolating the neural mechanisms of age-related changes in human working memory , 2000, Nature Neuroscience.

[35]  J. Deakin,et al.  Effects of lesions of the orbitofrontal cortex on sensitivity to delayed and probabilistic reinforcement , 2002, Psychopharmacology.

[36]  Kay M. Tye,et al.  Rapid strengthening of thalamo-amygdala synapses mediates cue–reward learning , 2008, Nature.

[37]  M. Roesch,et al.  Encoding of Time-Discounted Rewards in Orbitofrontal Cortex Is Independent of Value Representation , 2006, Neuron.

[38]  J. Pearce,et al.  The orienting response as an index of stimulus associability in rats. , 1988, Journal of experimental psychology. Animal behavior processes.

[39]  Geoffrey Schoenbaum,et al.  Encoding changes in orbitofrontal cortex in reversal-impaired aged rats. , 2006, Journal of neurophysiology.

[40]  Jeffrey W. Cooney,et al.  Top-down suppression deficit underlies working memory impairment in normal aging , 2005, Nature Neuroscience.

[41]  P. Holland,et al.  Orbitofrontal lesions impair use of cue-outcome associations in a devaluation task. , 2005, Behavioral neuroscience.

[42]  T. Kalenscher,et al.  Single Units in the Pigeon Brain Integrate Reward Amount and Time-to-Reward in an Impulsive Choice Task , 2005, Current Biology.

[43]  R J HERRNSTEIN,et al.  Relative and absolute strength of response as a function of frequency of reinforcement. , 1961, Journal of the experimental analysis of behavior.

[44]  J. Pearce,et al.  The strength of the orienting response during Pavlovian conditioning. , 1984, Journal of experimental psychology. Animal behavior processes.

[45]  T. Robbins,et al.  Contrasting Roles of Basolateral Amygdala and Orbitofrontal Cortex in Impulsive Choice , 2004, The Journal of Neuroscience.

[46]  D. Katz,et al.  Distinct Subtypes of Basolateral Amygdala Taste Neurons Reflect Palatability and Reward , 2009, The Journal of Neuroscience.

[47]  Samuel M. McClure,et al.  Age Differences in Striatal Delay Sensitivity during Intertemporal Choice in Healthy Adults , 2011, Front. Neurosci..

[48]  L Green,et al.  Temporal discounting in choice between delayed rewards: the role of age and income. , 1996, Psychology and aging.

[49]  R. Rescorla,et al.  The effect of two ways of devaluing the unconditioned stimulus after first- and second-order appetitive conditioning. , 1975, Journal of experimental psychology. Animal behavior processes.

[50]  H. Eichenbaum,et al.  Cognitive decline associated with normal aging in rats: a neuropsychological approach. , 1995, Learning & memory.

[51]  J. Evenden,et al.  The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement , 1996, Psychopharmacology.

[52]  C. Pennartz,et al.  Is a bird in the hand worth two in the future? The neuroeconomics of intertemporal decision-making , 2008, Progress in Neurobiology.

[53]  Geoffrey Schoenbaum,et al.  Different Roles for Orbitofrontal Cortex and Basolateral Amygdala in a Reinforcer Devaluation Task , 2003, The Journal of Neuroscience.

[54]  Guillem R. Esber,et al.  Attention-Related Pearce-Kaye-Hall Signals in Basolateral Amygdala Require the Midbrain Dopaminergic System , 2012, Biological Psychiatry.

[55]  R. Thaler Some empirical evidence on dynamic inconsistency , 1981 .

[56]  Joseph J. Paton,et al.  Moment-to-Moment Tracking of State Value in the Amygdala , 2008, The Journal of Neuroscience.