Abrupt Transitions between Prefrontal Neural Ensemble States Accompany Behavioral Transitions during Rule Learning

Durstewitz, Daniel; Vittoz, Nicole M.; Floresco, Stan; Seamans, Jeremy K.

doi:10.1016/j.neuron.2010.03.029

Cited by 334 publications

(358 citation statements)

References 51 publications

Supporting

Mentioning

327

Contrasting

Order By: Relevance

“…This concept aligns with studies indicating that an important role of the PFC is to generate contextappropriate behavior (23). Neurons recorded from PL exhibit context-specific responses (24), activity representing the rule or set being followed (25,26), activity signaling cues driving correct vs. incorrect behavior during an attention task (27), and delay-related firing rate changes influenced by the results (correct or error) in the incipient or previous trial (10). In the present study, context was defined as the specific response-outcome contingencies the animal experienced (i.e., RS press produces reward vs. RS press produces no reward), which corresponded with adaptive (high utility) behaviors (i.e., press to obtain reward vs. withhold pressing to decrease effort).…”

Section: Discussionsupporting

confidence: 86%

Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

Moorman

Aston‐Jones

2015

Proc. Natl. Acad. Sci. U.S.A.

131

View full text Add to dashboard Cite

The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/ prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior ("go") whereas ventral/ infralimbic (IL) mPFC is thought to control behavioral suppression ("stop"). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response-outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not.he prefrontal cortex (PFC) is involved in directing behavior and inhibiting inappropriate responses (1-4). Rodent medial PFC (mPFC) is functionally heterogeneous: prelimbic cortex (PL) is thought to be involved in behavioral execution, and infralimbic cortex (IL) in behavioral suppression, particularly during extinction (4). Fear conditioning studies support this dichotomy. PL stimulation elicits, and inactivation impairs, conditioned fear expression, and PL neurons fire during fear-related cues. Conversely, IL stimulation enhances, and inactivation blocks, extinction of fear conditioning, and IL neurons fire for extinguished cues that previously predicted an aversive stimulus (5, 6).A similar dichotomy is proposed for appetitive behaviors, although support for this is not unequivocal (7). PL inactivation during discriminative stimulus (DS)-driven reward-seeking reduces cue-driven behaviors (8). However, PL inactivation also increases nonspecific (8) and premature lever responding (9, 10), and PL is important in inhibiting responses during a stop-signal reaction time task (11). IL inactivation during DS task performance increases responses generally, including those triggered by a nonrewarded stimulus (NS) (8), increases premature responding on five-choice serial reaction time tasks (12), and increases spontaneous recovery and reinstatement (13). Cocaine seeking is also associated with activation ...

show abstract

Section: Discussionsupporting

confidence: 86%

Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

Moorman

Aston‐Jones

2015

Proc. Natl. Acad. Sci. U.S.A.

131

View full text Add to dashboard Cite

show abstract

“…Working memory is a process supported by neurons of various types organized into intricate microcircuits, which promote and sustain signal in a noisy background (Compte et al, 2000;Durstewitz et al, 2000b;Murray et al, 2014). Using a task that required the monkeys to represent one of the two saccade rules in working memory, we analyzed the effects of NMDA receptor blockade in the LPFC on the signal and noise in rule representation, which incorporates both the strength and the consistency in information representation.…”

Section: Discussionmentioning

confidence: 99%

“…The firing rates of all neurons in a given ensemble (i.e., all simultaneously recorded neurons in a single session) can be plotted in a multiple single-unit activity (MSUA) space (Durstewitz et al, 2010;Hyman et al, 2012), where an N ϫ 1 population activity vector (N is ensemble size) gives rise to a single point in the N-dimensional space. We defined ensemble SNR as the Mahalanobis distance (D Mah ) between the clusters of points in the MSUA space representing delay-period activities from prosaccade trials and antisaccade trials.…”

Section: Methodsmentioning

confidence: 99%

Ketamine-Induced Changes in the Signal and Noise of Rule Representation in Working Memory by Lateral Prefrontal Neurons

Ma¹,

Skoblenick²,

Seamans

et al. 2015

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

Working memory dysfunction is an especially debilitating symptom in schizophrenia. The NMDA antagonist ketamine has been successfully used to model working memory deficits in both rodents and nonhuman primates, but how it affects the strength and the consistency of working memory representations remains unclear. Here we recorded single-neuron activity in the lateral prefrontal cortex of macaque monkeys before and after the administration of subanesthetic doses of ketamine in a rule-based working memory task. The rule was instructed with a color cue before each delay period and dictated the correct prosaccadic or antisaccadic response to a peripheral stimulus appearing after the delay. We found that acute ketamine injections both weakened the rule signal across all delay periods and amplified the trial-to-trial variance in neural activities (i.e., noise), both within individual neurons and at the ensemble level, resulting in impaired performance. In the minority of postinjection trials when the animals responded correctly, the preservation of the signal strength during the delay periods was predictive of their subsequent success. Our findings suggest that NMDA receptor function may be critical for establishing the optimal signal-to-noise ratio in information representation by ensembles of prefrontal cortex neurons.

show abstract

“…Several studies have demonstrated how this can lead to a more informative analysis. For a rule-learning task in rats, Durstewitz et al (2010) found that neuronal activity recorded from the prefrontal cortex was in tight temporal relation to behavioral performance shifts in individuals. For the honeybee, two recent studies divided groups of identically treated animals into subgroups of .…”

Section: Implications For Data Analysismentioning

confidence: 99%

Average group behavior does not represent individual behavior in classical conditioning of the honeybee

Pamir¹,

Chakroborty²,

Stollhoff³

et al. 2011

Learn. Mem.

View full text Add to dashboard Cite

Conditioned behavior as observed during classical conditioning in a group of identically treated animals provides insights into the physiological process of learning and memory formation. However, several studies in vertebrates found a remarkable difference between the group-average behavioral performance and the behavioral characteristics of individual animals. Here, we analyzed a large number of data (1640 animals) on olfactory conditioning in the honeybee (Apis mellifera). The data acquired during absolute and differential classical conditioning differed with respect to the number of conditioning trials, the conditioned odors, the intertrial intervals, and the time of retention tests. We further investigated data in which animals were tested for spontaneous recovery from extinction. In all data sets we found that the gradually increasing group-average learning curve did not adequately represent the behavior of individual animals. Individual behavior was characterized by a rapid and stable acquisition of the conditioned response (CR), as well as by a rapid and stable cessation of the CR following unrewarded stimuli. In addition, we present and evaluate different model hypotheses on how honeybees form associations during classical conditioning by implementing a gradual learning process on the one hand and an all-or-none learning process on the other hand. In summary, our findings advise that individual behavior should be recognized as a meaningful predictor for the internal state of a honeybee-irrespective of the group-average behavioral performance.Learning and memory formation in vertebrates and invertebrates have been studied on the basis of a large range of classical and operant conditioning paradigms. Typically, the interpretation of experimental results relies on performance measures that were derived by averaging over behavioral observations from identically treated animals. However, several studies have recognized the inadequacy of group-average measures to capture the characteristics of individual behavior and, consequently, the learninginduced changes in individual brains (Krechevsky 1932;Restle 1965;Hanson and Killeen 1981;Estes 2002;Brown and Heathcote 2003;Cousineau et al. 2003). Most notably, Gallistel et al. (2004) found that the gradually increasing learning curve observed in many vertebrate learning paradigms reflected an artifact of group averaging. The behavioral performance of individuals appeared to be characterized by an abrupt and often step-like increase in the level of response.To our knowledge and in contrast to the vertebrate literature (see Gallistel et al. 2004), surprisingly little is known of a possibly heterogeneous expression of behavior for the most frequently applied invertebrate conditioning paradigms. For the fruit fly (Drosophila melanogaster) it appears to be common sense that the group-average behavioral measures adequately represent the probabilistic expression of behavior in individuals-a notion that goes back to an early study by Quinn et al. (1974).In the following,...

show abstract

Abrupt Transitions between Prefrontal Neural Ensemble States Accompany Behavioral Transitions during Rule Learning

Cited by 334 publications

References 51 publications

Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

Ketamine-Induced Changes in the Signal and Noise of Rule Representation in Working Memory by Lateral Prefrontal Neurons

Average group behavior does not represent individual behavior in classical conditioning of the honeybee

Contact Info

Product

Resources

About