A silent eligibility trace enables dopamine-dependent synaptic plasticity for reinforcement learning in the mouse striatum.

Dopamine-dependent synaptic plasticity is a candidate mechanism for reinforcement learning. A silent eligibility trace - initiated by synaptic activity and transformed into synaptic strengthening by later action of dopamine - has been hypothesized to explain the retroactive effect of dopamine in reinforcing past behaviour. We tested this hypothesis by measuring time-dependent modulation of synaptic plasticity by dopamine in adult mouse striatum, using whole-cell recordings. Presynaptic activity followed by postsynaptic action potentials (pre-post) caused spike-timing-dependent long-term depression in D1-expressing neurons, but not in D2 neurons, and not if postsynaptic activity followed presynaptic activity. Subsequent experiments focused on D1 neurons. Applying a dopamine D1 receptor agonist during induction of pre-post plasticity caused long-term potentiation. This long-term potentiation was hidden by long-term depression occurring concurrently and was unmasked when long-term depression blocked an L-type calcium channel antagonist. Long-term potentiation was blocked by a Ca2+ -permeable AMPA receptor antagonist but not by an NMDA antagonist or an L-type calcium channel antagonist. Pre-post stimulation caused transient elevation of rectification - a marker for expression of Ca2+ -permeable AMPA receptors - for 2-4-s after stimulation. To test for an eligibility trace, dopamine was uncaged at specific time points before and after pre- and postsynaptic conjunction of activity. Dopamine caused potentiation selectively at synapses that were active 2-s before dopamine release, but not at earlier or later times. Our results provide direct evidence for a silent eligibility trace in the synapses of striatal neurons. This dopamine-timing-dependent plasticity may play a central role in reinforcement learning.

Resting energy expenditure (REE) in six- to seventeen-year-old Japanese children and adolescents.

Accurate estimation of resting energy expenditure (REE) in children and adolescents is important to establish estimated energy requirements for the Japanese population. Our objectives were 1) to determine the REE of 6- to 17-y-old Japanese children and adolescents by indirect calorimetry in order to estimate energy expenditure for this group, 2) to compare measured REE with predicted REE to determine the accuracy of predictive equations of REE for Japanese children and adolescents, and 3) to derive new predictive equations for REE for Japanese children and adolescents based on measured REE. REE was measured in 221 Japanese children and adolescents, aged 6 to 17 y old (113 boys and 108 girls) using a ventilated indirect calorimeter. Anthropometric and body composition measurements were also performed. REE expressed as absolute values increased with age in both genders, and there was a significant difference between genders in the 12-17 y age group. REE was strongly correlated with body weight (BW) and fat-free mass (FFM). REE adjusted for BW or FFM decreased with age in both genders, and a gender difference was still observed in the 12-17 y age group after this adjustment. The highest accuracy of prediction was achieved using the Dietary Reference Intake for Japanese (1969) for boys and the Molnar equation for girls. Step-down multiple regression analysis was carried out using either a combination of age, gender, BW, and height, or a combination of age, gender, FFM, and fat mass (FM). The predictive equation accounted for 75% (R2) and 76% of the variance, respectively. In conclusion, absolute REE increased and REE adjusted for BW or FFM decreased with age. The major determinant of REE was FFM, but significant gender differences were observed in the 12-17 y range for both absolute REE and adjusted REE.

Lateral entorhinal cortex is necessary for associative but not nonassociative recognition memory.

The lateral entorhinal cortex (LEC) provides one of the two major input pathways to the hippocampus and has been suggested to process the nonspatial contextual details of episodic memory. Combined with spatial information from the medial entorhinal cortex it is hypothesised that this contextual information is used to form an integrated spatially selective, context-specific response in the hippocampus that underlies episodic memory. Recently, we reported that the LEC is required for recognition of objects that have been experienced in a specific context (Wilson et al. (2013) Hippocampus 23:352-366). Here, we sought to extend this work to assess the role of the LEC in recognition of all associative combinations of objects, places and contexts within an episode. Unlike controls, rats with excitotoxic lesions of the LEC showed no evidence of recognizing familiar combinations of object in place, place in context, or object in place and context. However, LEC lesioned rats showed normal recognition of objects and places independently from each other (nonassociative recognition). Together with our previous findings, these data suggest that the LEC is critical for associative recognition memory and may bind together information relating to objects, places, and contexts needed for episodic memory formation.

Lateral entorhinal cortex is critical for novel object-context recognition.

Episodic memory incorporates information about specific events or occasions including spatial locations and the contextual features of the environment in which the event took place. It has been modeled in rats using spontaneous exploration of novel configurations of objects, their locations, and the contexts in which they are presented. While we have a detailed understanding of how spatial location is processed in the brain relatively little is known about where the nonspatial contextual components of episodic memory are processed. Initial experiments measured c-fos expression during an object-context recognition (OCR) task to examine which networks within the brain process contextual features of an event. Increased c-fos expression was found in the lateral entorhinal cortex (LEC; a major hippocampal afferent) during OCR relative to control conditions. In a subsequent experiment it was demonstrated that rats with lesions of LEC were unable to recognize object-context associations yet showed normal object recognition and normal context recognition. These data suggest that contextual features of the environment are integrated with object identity in LEC and demonstrate that recognition of such object-context associations requires the LEC. This is consistent with the suggestion that contextual features of an event are processed in LEC and that this information is combined with spatial information from medial entorhinal cortex to form episodic memory in the hippocampus.