David R. Euston

The role of medial prefrontal cortex in memory and decision making.

Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation.

Fast-Forward Playback of Recent Memory Sequences in Prefrontal Cortex During Sleep

As previously shown in the hippocampus and other brain areas, patterns of firing-rate correlations between neurons in the rat medial prefrontal cortex during a repetitive sequence task were preserved during subsequent sleep, suggesting that waking patterns are reactivated. We found that, during sleep, reactivation of spatiotemporal patterns was coherent across the network and compressed in time by a factor of 6 to 7. Thus, when behavioral constraints are removed, the brains intrinsic processing speed may be much faster than it is in real time. Given recent evidence implicating the medial prefrontal cortex in retrieval of long-term memories, the observed replay may play a role in the process of memory consolidation.

Sequential-Context-Dependent Hippocampal Activity Is Not Necessary to Learn Sequences with Repeated Elements

Learning sequences of events (e.g., a-b-c) is conceptually a simple problem that can be solved using asymmetrically linked cell assemblies [e.g., “phase sequences” (Hebb, 1949)], provided that the elements of the sequence are unique. When elements repeat within the sequence, however (e.g., a-b-c-d-b-e), the same element belongs to two separate “contexts,” and a more complex sequence encoding mechanism is required to differentiate between the two contexts. Some neural structure must form sequential-context-dependent, or “differential,” representations of the two contexts (i.e., b as an element of “a-b-c” as opposed to “d-b-e”) to allow the correct choice to be made after the repeated element. To investigate the possible role of hippocampus in complex sequence encoding, rats were trained to remember repeated-location sequences under three conditions: (1) reward was given at each location; (2) during training, moveable barriers were placed at the entry and exit of the repeated segment to direct the rat and were removed once the sequence was learned; and (3) reward was withheld at the entry and exit of the repeated segment. In the first condition, hippocampal ensemble activity did not differentiate the sequential context of the repeated segment, indicating that complex sequences with repeated segments can be learned without differential encoding within the hippocampus. Differential hippocampal encoding was observed, however, under the latter two conditions, suggesting that long-term memory for discriminative cues present only during training, working memory of the most recently visited reinforcement sites, or anticipation of the subsequent reinforcement site can separate hippocampal activity patterns at the same location.

Stored-trace reactivation in rat prefrontal cortex is correlated with down-to-up state fluctuation density

Spontaneous reactivation of previously stored patterns of neural activity occurs in hippocampus and neocortex during non-rapid eye movement (NREM) sleep. Notable features of the neocortical local field potential during NREM sleep are high-amplitude, low-frequency thalamocortical oscillations including K-complexes, low-voltage spindles, and high-voltage spindles. Using combined neuronal ensemble and local field potential recordings, we show that prefrontal stored-trace reactivation is correlated with the density of down-to-up state transitions of the population of simultaneously recorded cells, as well as K-complexes and low-voltage spindles in the local field potential. This result strengthens the connection between reactivation and learning, as these same NREM sleep features have been correlated with memory. Although memory trace reactivation is correlated with low-voltage spindles, it is not correlated with high-voltage spindles, indicating that despite their similar frequency characteristics, these two oscillations serve different functions.

Apparent Encoding of Sequential Context in Rat Medial Prefrontal Cortex Is Accounted for by Behavioral Variability

Simple sequences can be represented via asymmetrically linked neural assemblies, provided that the elements of the sequence are unique. When elements repeat, however (e.g., A-B-C-B-A), the same element belongs to two separate “sequential contexts,” and a more complex encoding mechanism is required. To enable correct sequence performance, some neural structure must provide a disambiguating signal that differentiates the two sequential contexts (i.e., B as an element of “A-B” as opposed to “C-B”). The disambiguating signal may derive from a form of working memory, or, in some cases, a simple timing mechanism may suffice. To investigate the possible role of medial prefrontal cortex in complex sequence encoding, rats were trained on a spatial sequence containing two adjacent repeated segments (e.g., A-B-C-D-B-C-E). The double-repeat procedure minimized behavioral differences in the second leg (C) of the repeat subsequence that arise in the first leg (B) because of differences in the entry point (e.g., A-B vs D-B). Far more cells were context sensitive along the first leg than along the second (36 vs 9%), and most of the differences were accounted for by systematic variations in the rats trajectory, which were much larger along the first leg. There is thus little evidence for sequential context-discriminative activity in the medial prefrontal cortex that cannot plausibly be accounted for by context-dependent behavior. The finding that the rodent medial prefrontal cortex is highly sensitive to sensory–behavioral variables raises doubts about previous experiments that purport to show working memory-related activity in this region.

The synthesis and use of the owl's auditory space map

Abstract.The barn owl (Tyto alba) is capable of capturing prey by passive hearing alone, guided by a topographic map of auditory space in the external nucleus of its inferior colliculus. The neurons of this auditory space map have discrete spatial receptive fields that result from the computation of interaural differences in the level (ILD) and time-of-arrival (ITD) of sounds. Below we review the synthesis of the spatial receptive fields from the frequency-specific ITDs and ILDs to which the neurons are tuned, concentrating on recent studies exploiting virtual auditory space techniques to analyze the contribution of ILD. We then compared the owl’s spatial discrimination, assessed behaviorally, with that of its space map neurons. Spatial discrimination was assessed using a novel paradigm involving the pupillary dilation response (PDR), and neuronal acuity was assessed by measuring the changes in firing rate resulting from changes in source location, scaled to the variance. This signal-detection-based approach revealed that the change in the position of the neural image on this map best explains the spatial discrimination measured using the PDR. We compare this result to recent studies in mammalian systems.

Are 50-kHz calls used as play signals in the playful interactions of rats? II. Evidence from the effects of devocalization.

During playful interactions, juvenile rats emit many 50-kHz ultrasonic vocalizations, which are associated with a positive affective state. In addition, these calls may also serve a communicative role - as play signals that promote playful contact. Consistent with this hypothesis, a previous study found that vocalizations are more frequent prior to playful contact than after contact is terminated. The present study uses devocalized rats to test three predictions arising from the play signals hypothesis. First, if vocalizations are used to facilitate contact, then in pairs of rats in which one is devocalized, the higher frequency of pre-contact calling should only be present when the intact rat is initiating the approach. Second, when both partners in a playing pair are devocalized, the frequency of play should be reduced and the typical pattern of playful wrestling disrupted. Finally, when given a choice to play with a vocal and a non-vocal partner, rats should prefer to play with the one able to vocalize. The second prediction was supported in that the frequency of playful interactions as well as some typical patterns of play was disrupted. Even though the data for the other two predictions did not produce the expected findings, they support the conclusion that, in rats, 50-kHz calls are likely to function to maintain a playful mood and for them to signal to one another during play fighting.

Are 50-kHz calls used as play signals in the playful interactions of rats? I. Evidence from the timing and context of their use.

During playful interactions, rats emit increased levels of 50-kHz vocalizations. It is possible that these vocalizations are used as play signals that promote and maintain playful contact. The study investigated this possibility. It was predicted that if these vocalizations are used as play signals, they should be more prevalent (1) before an attack, (2) in attacks leading to wrestling, and (3) in males compared to females, as males play more roughly. Moreover, given that there are at least 15 different subtypes of 50-kHz calls, it is possible that different calls are used in different contexts. Therefore, our prediction (4) was that different subtypes would be used for initiating and terminating playful contact. Pairs of same-sex juveniles were tested so that video recordings of their play and audio recordings of their vocalizations were synchronized. 50-kHz vocalizations occur more often before an attack and in male pairs. Specific calls were associated with specific types of behaviors and these associations differed between male and female rats. However, calls were not more frequent in attacks leading to wrestling than in attacks leading to withdrawal. The data provide qualified support for the hypothesis that 50-kHz vocalizations function as play signals.

Lesions of dorsal striatum eliminate lose-switch responding but not mixed-response strategies in rats.

We used focal brain lesions in rats to examine how dorsomedial (DMS) and dorsolateral (DLS) regions of the striatum differently contribute to response adaptation driven by the delivery or omission of rewards. Rats performed a binary choice task under two modes: one in which responses were rewarded on half of the trials regardless of choice; and another ‘competitive’ one in which only unpredictable choices were rewarded. In both modes, control animals were more likely to use a predictable lose‐switch strategy than animals with lesions of either DMS or DLS. Animals with lesions of DMS presumably relied more on DLS for behavioural control, and generated repetitive responses in the first mode. These animals then shifted to a random response strategy in the competitive mode, thereby performing better than controls or animals with DLS lesions. Analysis using computational models of reinforcement learning indicated that animals with striatal lesions, particularly of the DLS, had blunted reward sensitivity and less stochasticity in the choice mechanism. These results provide further evidence that the rodent DLS is involved in rapid response adaptation that is more sophisticated than that embodied by the classic notion of habit formation driven by gradual stimulus–response learning.

Are 50-khz calls used as play signals in the playful interactions of rats? III. The effects of devocalization on play with unfamiliar partners as juveniles and as adults

When playing, rats emit 50-kHz calls which may function as play signals. A previous study using devocalized rats provides support for the hypothesis that 50-kHz function to promote and maintain playful interactions (Kisko et al., 2015). However, in that study, all pairs were cage mates and familiar with each others playful tendencies that could have attenuated the role of play signals. The present study uses unfamiliar pairs to eliminate any chance for such attenuation. Four hypotheses about how 50-kHz calls could act as play signals were tested, that (1) they maintain the playful mood of the partner, (2) they are used to locate partners, (3) they attract play partners and (4) they reduce the risk of playful encounters from escalating to serious fights. Predictions arising from the first three hypotheses, tested in juveniles, were not supported, suggesting that, for juveniles, 50-kHz calls are not facilitating playful interactions as play signals. The fourth hypothesis, however, was supported in adults, but not in juveniles, in that unfamiliar adult males were more likely to escalate playful encounters into serious fights when one partner was devocalized. These findings suggest that vocalizations at most have a minor role in juvenile play but serve a more central role in modulating adult interactions between strangers, allowing for the tactical mitigation of the risk of aggression.