Cracking and Packing Information about the Features of Expected Rewards in the Orbitofrontal Cortex.

The orbitofrontal cortex (OFC) is crucial for tracking various aspects of expected outcomes, thereby helping to guide choices and support learning. Our previous study showed that the effects of reward timing and size on the activity of single units in OFC were dissociable when these attributes were manipulated independently ( Roesch et al., 2006). However, in real-life decision-making scenarios, outcome features often change simultaneously, so here we investigated how OFC neurons in male rats integrate information about the timing and identity (flavor) of reward and respond to changes in these features, according to whether they were changed simultaneously or separately. We found that a substantial number of OFC neurons fired differentially to immediate versus delayed reward and to the different reward flavors. However, contrary to the previous study, selectivity for timing was strongly correlated with selectivity for identity. Taken together with the previous research, these results suggest that when reward features are correlated, OFC tends to "pack" them into unitary constructs, whereas when they are independent, OFC tends to "crack" them into separate constructs. Furthermore, we found that when both reward timing and flavor were changed, reward-responsive OFC neurons showed unique activity patterns preceding and during the omission of an expected reward. Interestingly, this OFC activity is similar and slightly preceded the ventral tegmental area dopamine (VTA DA) activity observed in a previous study ( Takahashi et al., 2023), consistent with the role of OFC in providing predictive information to VTA DA neurons.

Scalable representation of time in the hippocampus.

Hippocampal "time cells" encode specific moments of temporally organized experiences that may support hippocampal functions for episodic memory. However, little is known about the reorganization of the temporal representation of time cells during changes in temporal structures of episodes. We investigated CA1 neuronal activity during temporal bisection tasks, in which the sets of time intervals to be discriminated were designed to be extended or contracted across the blocks of trials. Assemblies of neurons encoded elapsed time during the interval, and the representation was scaled when the set of interval times was varied. Theta phase precession and theta sequences of time cells were also scalable, and the fine temporal relationships were preserved between pairs in theta cycles. Moreover, theta sequences reflected the rats' decisions on the basis of their time estimation. These findings demonstrate that scalable features of time cells may support the capability of flexible temporal representation for memory formation.

Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits.

Left-right asymmetry is known to exist at several anatomical levels in the brain and recent studies have provided further evidence to show that it also exists at a molecular level in the hippocampal CA3-CA1 circuit. The distribution of N-methyl-d-aspartate (NMDA) receptor NR2B subunits in the apical and basal synapses of CA1 pyramidal neurons is asymmetrical if the input arrives from the left or right CA3 pyramidal neurons. In the present study, we examined the role of hippocampal asymmetry in cognitive function using ß2-microglobulin knock-out (ß2m KO) mice, which lack hippocampal asymmetry. We tested ß2m KO mice in a series of spatial and non-spatial learning tasks and compared the performances of ß2m KO and C57BL6/J wild-type (WT) mice. The ß2m KO mice appeared normal in both spatial reference memory and spatial working memory tasks but they took more time than WT mice in learning the two non-spatial learning tasks (i.e., a differential reinforcement of lower rates of behavior (DRL) task and a straight runway task). The ß2m KO mice also showed less precision in their response timing in the DRL task and showed weaker spontaneous recovery during extinction in the straight runway task. These results indicate that hippocampal asymmetry is important for certain characteristics of non-spatial learning.