Motivated to time: Effects of reinforcer devaluation and opportunity cost on interval timing.

Prior research suggests that interval timing performance is sensitive to reinforcer devaluation effects and to the rate of competing sources of reinforcement. The present study sought to replicate and account for these findings in rats. A self-paced concurrent fixed-interval (FI) random-ratio (RR) schedule of reinforcement was implemented in which the FI requirement varied across training conditions (12, 24, 48 s). The RR requirement-which imposed an opportunity cost to responding on the FI component-was adjusted so that it took about twice the FI requirement, on average, to complete it. Probe reinforcer devaluation (prefeeding) sessions were conducted at the end of each condition. To assess the effect of contextual reinforcement on timing performance, the RR requirement was removed before the end of the experiment. Consistent with prior findings, performance on the FI component tracked schedule requirement and displayed scalar invariance; the removal of the RR component yielded more premature FI responses. For some rats, prefeeding reduced the number of trials initiated without affecting timing performance; for other rats, prefeeding delayed responding on the FI component but had a weaker effect on trial initiation. These results support the notion that timing and motivational processes are separable, suggesting novel explanations for ostensible motivational effects on timing performance.

Assessing complex odor discrimination in mice using a novel instrumental patterning task.

Negative patterning tasks are a key tool to unveil the mechanisms by which stimulus representations are acquired-a central concern in Robert Rescorla's research. In these tasks, target stimuli are reinforced when presented individually (A+/B+) but not when presented in compound (AB-). The discrimination of single stimuli from their compound presentation is a challenge for theories of associative learning, because it cannot be explained by the simple accrual of associative strength. The present study examined the conditions under which mice learn this part-whole discrimination in olfactory stimuli using a novel instrumental methodology. In two experiments, reinforcement was contingent on distinct responses depending on whether a set of odor mixtures were presented in isolation or as a compound. Using C57BL/6 mice, Experiment 1 showed a mutual interference between learning a response to individual odors and learning a different response to those odors presented in compound. Using wild-type APP/PS1 mice (a control strain for a murine model of Alzheimer's disease), Experiment 2 replicated this interference and showed that it is stimulus-specific. These experiments show that the instrumental patterning task may not only complement Pavlovian negative patterning tasks but may also motivate its own questions on the representation of complex stimuli. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.

Many developmental syndromes have been linked to genetic mutations that cause abnormal ERK/MAPK activity; however, the neuropathological effects of hyperactive signaling are not fully understood. Here, we examined whether hyperactivation of MEK1 modifies the development of GABAergic cortical interneurons (CINs), a heterogeneous population of inhibitory neurons necessary for cortical function. We show that GABAergic-neuron specific MEK1 hyperactivation in vivo leads to increased cleaved caspase-3 labeling in a subpopulation of immature neurons in the embryonic subpallial mantle zone. Adult mutants displayed a significant loss of parvalbumin (PV), but not somatostatin, expressing CINs and a reduction in perisomatic inhibitory synapses on excitatory neurons. Surviving mutant PV-CINs maintained a typical fast-spiking phenotype but showed signs of decreased intrinsic excitability that coincided with an increased risk of seizure-like phenotypes. In contrast to other mouse models of PV-CIN loss, we discovered a robust increase in the accumulation of perineuronal nets, an extracellular structure thought to restrict plasticity. Indeed, we found that mutants exhibited a significant impairment in the acquisition of behavioral response inhibition capacity. Overall, our data suggest PV-CIN development is particularly sensitive to hyperactive MEK1 signaling, which may underlie certain neurological deficits frequently observed in ERK/MAPK-linked syndromes.

On the Appropriate Measure to Estimate Hyperbolic Discounting Rate (K) using the Method of Least Squares.

The estimation of the rate at which value declines with delay requires identifying the correct discounting model, applying the appropriate parameter estimation method, and choosing the dependent measure from which parameters are estimated. The simplest adequate discounting model is the hyperbolic model; the simplest method to estimate its sole free parameter, K, is the method of least squares. Estimates of K based on relative subjective values (RSV), although typical, are not necessarily more reliable than those obtained through other measures. We consider an alternative measure termed immediacy premium (IP): the ratio of value lost over value preserved due to outcome delay. According to hyperbolic discounting, IP is a linear function of delay. As a result, estimates of K obtained from IP circumvent the divergence between individual and aggregate estimates obtained with the RSV method. Moreover, published data suggests that estimates of K based on RSV and IP differ systematically in humans and in pigeons. Regardless of the dependent measure adopted, estimates of K obtained from nonhuman animals, but not from humans, yield residuals that conform with error-distribution assumptions of the method of least squares. Although residuals obtained using the IP method in human data diverged more from normality than those obtained using the RSV method, the sequential dependence over delays of the former was weaker than that of the latter. We therefore recommend adopting both RSV and IP when estimating hyperbolic K using the method of least squares, resorting to more elaborate estimation methods when inferences drawn from these estimates are inconsistent.

The differential role of the dorsal hippocampus in initiating and terminating timed responses: A lesion study using the switch-timing task.

This study investigated the role of the dorsal hippocampus (dHPC) in the temporal entrainment of behavior, while addressing limitations of previous evidence from peak procedure experiments. Rats were first trained on a switch-timing task in which food was obtained from one of two concurrently available levers; one lever was effective after 8 s and the other after 16  s. After performance stabilized, rats underwent either bilateral NMDA lesions of the dHPC or sham lesions. After recovery, switch-timing training resumed. In a subsequent condition, the switch-timing task was modified such that food was available after either 8 or 32 s. Although dHPC lesions had subtle and complex effects on when rats stopped seeking for food at the 8-s lever (departures), it more systematically reduced the time when rats started seeking for food at the 16-s and 32-s lever (switches). No systematic effect of dHPC lesions were observed on the coefficient of quartile variation (normalized dispersion) of latencies to switch. Within the context of the pacemaker-accumulator framework of interval timing, these findings suggest that partially or wholly independent mechanisms control the initiation and termination of timed responses, and that the dHPC is primarily involved in encoding the time to start responding.