Inactivation of medial prefrontal cortex impairs time interval discrimination in rats (original) (raw)
Related papers
Neural Correlates of Interval Timing in Rodent Prefrontal Cortex
Journal of Neuroscience, 2013
Time interval estimation is involved in numerous behavioral processes, but its underlying neural mechanisms remain unclear. In particular, it has been controversial whether time is encoded on a linear or logarithmic scale. Based on our previous finding that inactivation of the medial prefrontal cortex (mPFC) profoundly impairs rat's ability to discriminate time intervals, we investigated how the mPFC processes temporal information by examining activity of mPFC neurons in rats performing a temporal bisection task. Many mPFC neurons conveyed temporal information based on monotonically changing activity profiles over time with negative accelerations, so that their activity profiles were better described by logarithmic than linear functions. Moreover, the precision of time-interval discrimination based on neural activity was lowered in proportion to the elapse of time, but without proportional increase in neural variability, which is well accounted for by logarithmic, but not by linear functions. As a population, mPFC neurons conveyed precise information about the elapse of time with their activity tightly correlated with the animal's choice of target. These results suggest that the mPFC might be part of an internal clock in charge of controlling interval-timing behavior, and that linearly changing neuronal activity on a logarithmic time scale might be one way of representing the elapse of time in the brain.
Bio-protocol, 2020
Animals keep track of time intervals in the seconds to minutes range with, on average, high accuracy but substantial trial-to-trial variability. The ability to detect the statistical signatures of such timing behavior is an indispensable feature of a good and theoretically-tractable testing procedure. A widely used interval timing procedure is the peak interval (PI) procedure, where animals learn to anticipate rewards that become available after a fixed delay. After learning, they cluster their responses around that reward-availability time. The in-depth analysis of such timed anticipatory responses leads to the understanding of an internal timing mechanism, that is, the processing dynamics and systematic biases of the brain’s clock. This protocol explains in detail how the PI procedure can be implemented in rodents, from training through testing to analysis. We showcase both trial-by-trial and trial-averaged analytical methods as a window into these internal processes. This protocol has the advantages of capturing timing behavior in its full-complexity in a fashion that allows for a theoretical treatment of the data.
Frontiers in integrative neuroscience, 2018
Motor sequence learning, planning and execution of goal-directed behaviors, and decision making rely on accurate time estimation and production of durations in the seconds-to-minutes range. The pathways involved in planning and execution of goal-directed behaviors include cortico-striato-thalamo-cortical circuitry modulated by dopaminergic inputs. A critical feature of interval timing is its scalar property, by which the precision of timing is proportional to the timed duration. We examined the role of medial prefrontal cortex (mPFC) in timing by evaluating the effect of its reversible inactivation on timing accuracy, timing precision and scalar timing. Rats were trained to time two durations in a peak-interval (PI) procedure. Reversible mPFC inactivation using GABA agonist muscimol resulted in decreased timing precision, with no effect on timing accuracy and scalar timing. These results are partly at odds with studies suggesting that ramping prefrontal activity is crucial to timing...
Interval timing in rats: tracking unsignaled changes in the fixed interval schedule requirement
Behavioural Processes, 2002
The present experiment examined interval timing in rats under dynamic conditions. A session began with FI60 s intervals, changed to a FI20 s, FI30 s, or FI40 s schedule at an unpredictable point, and then returned to a FI60 s schedule after the rats received 1, 8, or 24 successive short FI intervals. Variations in the duration and number of shorter intervals occurred across sessions and conditions. We observed rapid control of wait time duration by the FI duration of the preceding interval (one-back tracking), and changes in wait time depended on the number and duration of the shorter intervals. Furthermore, we observed proportional and scalar timing effects in overall wait time duration. The results provide information about the relation between interval timing under dynamic and steady state conditions. (J.J. Higa). 0376-6357/02/$ -see front matter © 2002 Elsevier Science B.V. All rights reserved. PII: S 0 3 7 6 -6 3 5 7 ( 0 2 ) 0 0 0 2 9 -3
Multiple-interval timing in rats: Performance on two-valued mixed fixed-interval schedules.
2003
Abstract 1. Three experiments studied timing in rats on 2-valued mixed-fixed-interval schedules, with equally probable components, Fixed-Interval S and Fixed-Interval L (FI S and FI L, respectively). When the L: S ratio was greater than 4, 2 distinct response peaks appeared close to FI S and FI L, and data could be well fitted by the sum of 2 Gaussian curves.
Journal of the Experimental Analysis of Behavior, 1992
Killeen and Fetterman's (1988) behavioral theory of animal timing predicts that decreases in the rate of reinforcement should produce decreases in the sensitivity (A') of temporal discriminations and a decrease in miss and correct rejection rates (decrease in bias toward "long" responses). Eight rats were trained on a 10-versus 0.1-s temporal discrimination with an intertrial interval of 5 s and were subsequently tested on probe days on the same discrimination with intertrial intervals of 1, 2.5, 5, 10, or 20 s. The rate of reinforcement declined for all animals as intertrial interval increased. Although sensitivity (A') decreased with increasing intertrial interval, all rats showed an increase in bias to make long responses.
Rapid timing of a single transition in interfood interval duration by rats
Animal Learning & Behavior, 1997
The present experiment examined temporal control of wait-time responses by interfood interval (IFI) duration. We exposed rats to a sequence of intervals that changed in duration at an unpredictable point within a session. In Phase 1, intervals changed from 15 to 5 sec (step-down) or from 15 to 45 sec (step-up). In Phase 2, we increased the intervals by a factor of four. We observed rapid timing effects during a transition in both phases of the experiment: A step-down and a step-up transition significantly decreased and increased wait time in the next interval, respectively. Furthermore, adjustment of wait times during step-down was largely complete by the third transition IFl. In contrast, wait times gradually increased across several transition IFls during step-up. The results reveal dynamic properties of temporal control that depend on the direction in which IFIs change. Organization ofbehavior by the time between food presentations has been demonstrated in a variety of animals ranging from rats and pigeons (see, e.g., Richelle & Lejeune, 1980) to captive starlings (e.g., Brunner, Kacelnik, & Gibbon, 1992) to fish and turtles (Lejeune & Wearden, 1991). For example, animals given extended exposure to fixed-interval (FI) reinforcement schedules come under the control of the time between reinforcer deliveries (interfood interval, IFI). A hallmark of responding during FI schedules is a postreinforcement wait time that is proportional to the IFI duration (Lowe & Harzem, 1977; Shull, 1970; Zeiler & Powell, 1994). FI schedules and other timing procedures (e.g., the peak procedure; Catania, 1970; Roberts, 1981) are usually studied for the steady-state behavior they generate. Many quantitative properties have been discovered (e.g., scalar timing; Gibbon, 1977) that have been useful in testing and developing models of timing. Leading models in this area are scalar expectancy theory (SET; Church, 1984; Gibbon, 1977; Gibbon & Church, 1984) and the behavioral theory of timing (BeT; Killeen & Fetterman, 1988). Both are essentially molar models. SET's assumption about memory for time intervals, for example, is based on statistical distributions derived from molar features of a pacemaker system and reinforcement schedule (e.g., Gibbon, 1991, 1995; Gibbon & Church, 1984). BeT, too, is based on molar properties. According to BeT, adjunctive responses mediate time discrimination, and these responses are assumed to be associated with transitions be
Interval timing in genetically modified mice: a simple paradigm
Genes, Brain and Behavior, 2008
We describe a behavioral screen for the quantitative study of interval timing and interval memory in mice. Mice learn to switch from a short-latency feeding station to a long-latency station when the short latency has passed without a feeding. The psychometric function is the cumulative distribution of switch latencies. Its median measures timing accuracy and its interquartile interval measures timing precision. Next, using this behavioral paradigm, we have examined mice with a gene knockout of the receptor for gastrin-releasing peptide that show enhanced (i.e. prolonged) freezing in fear conditioning. We have tested the hypothesis that the mutants freeze longer because they are more uncertain than wild types about when to expect the electric shock. The knockouts however show normal accuracy and precision in timing, so we have rejected this alternative hypothesis. Last, we conduct the pharmacological validation of our behavioral screen using D-amphetamine and methamphetamine. We suggest including the analysis of interval timing and temporal memory in tests of genetically modified mice for learning and memory and argue that our paradigm allows this to be done simply and efficiently.
Biasing temporal judgments in rats, pigeons, and humans
Models of interval timing typically include a response threshold to account for temporal production. The present study sought to evaluate the dependent concurrent fixed-interval fixed-interval schedule of reinforcement as a tool for selectively isolating the response threshold in rats, pigeons, and humans. In this task, reinforcement is available either at one location after a short delay or at another location at a longer delay. Because the reinforced location is not signaled, subjects normally respond on the first location and, if reinforcement is not delivered, then switch to the second location. The latency to switch between locations served as the primary dependent measure. After training rats, pigeons, and humans with equal reinforcement magnitudes in the short and long delays, the magnitude of reinforcement was increased threefold on the long-delay location. Consistent with model predictions, this biasing procedure decreased estimates of the response threshold of rats and pigeons, but also reduced temporal control in these species and increased response-threshold estimates in humans. Human and pigeon performance also suggested a magnitude-induced increase in the speed of the internal clock. Collectively, these results suggest that differences in reinforcement magnitude between response alternatives appear to modulate the response threshold, but not selectively, and may provide guidance for better isolating response threshold effects in humans.