Coordinating brain-distributed network activities in memory resistant to extinction.

Certain memories resist extinction to continue invigorating maladaptive actions. The robustness of these memories could depend on their widely distributed implementation across populations of neurons in multiple brain regions. However, how dispersed neuronal activities are collectively organized to underpin a persistent memory-guided behavior remains unknown. To investigate this, we simultaneously monitored the prefrontal cortex, nucleus accumbens, amygdala, hippocampus, and ventral tegmental area (VTA) of the mouse brain from initial recall to post-extinction renewal of a memory involving cocaine experience. We uncover a higher-order pattern of short-lived beta-frequency (15-25 Hz) activities that are transiently coordinated across these networks during memory retrieval. The output of a divergent pathway from upstream VTA glutamatergic neurons, paced by a slower (4-Hz) oscillation, actuates this multi-network beta-band coactivation; its closed-loop phase-informed suppression prevents renewal of cocaine-biased behavior. Binding brain-distributed neural activities in this temporally structured manner may constitute an organizational principle of robust memory expression.

Organizing the coactivity structure of the hippocampus from robust to flexible memory.

New memories are integrated into prior knowledge of the world. But what if consecutive memories exert opposing demands on the host brain network? We report that acquiring a robust (food-context) memory constrains the mouse hippocampus within a population activity space of highly correlated spike trains that prevents subsequent computation of a flexible (object-location) memory. This densely correlated firing structure developed over repeated mnemonic experience, gradually coupling neurons in the superficial sublayer of the CA1 stratum pyramidale to whole-population activity. Applying hippocampal theta-driven closed-loop optogenetic suppression to mitigate this neuronal recruitment during (food-context) memory formation relaxed the topological constraint on hippocampal coactivity and restored subsequent flexible (object-location) memory. These findings uncover an organizational principle for the peer-to-peer coactivity structure of the hippocampal cell population to meet memory demands.

The deep and slow breathing characterizing rest favors brain respiratory-drive.

A respiration-locked activity in the olfactory brain, mainly originating in the mechano-sensitivity of olfactory sensory neurons to air pressure, propagates from the olfactory bulb to the rest of the brain. Interestingly, changes in nasal airflow rate result in reorganization of olfactory bulb response. By leveraging spontaneous variations of respiratory dynamics during natural conditions, we investigated whether respiratory drive also varies with nasal airflow movements. We analyzed local field potential activity relative to respiratory signal in various brain regions during waking and sleep states. We found that respiration regime was state-specific, and that quiet waking was the only vigilance state during which all the recorded structures can be respiration-driven whatever the respiratory frequency. Using CO2-enriched air to alter respiratory regime associated to each state and a respiratory cycle based analysis, we evidenced that the large and strong brain drive observed during quiet waking was related to an optimal trade-off between depth and duration of inspiration in the respiratory pattern, characterizing this specific state. These results show for the first time that changes in respiration regime affect cortical dynamics and that the respiratory regime associated with rest is optimal for respiration to drive the brain.

Integrating new memories into the hippocampal network activity space.

By investigating the topology of neuronal co-activity, we found that mnemonic information spans multiple operational axes in the mouse hippocampus network. High-activity principal cells form the core of each memory along a first axis, segregating spatial contexts and novelty. Low-activity cells join co-activity motifs across behavioral events and enable their crosstalk along two other axes. This reveals an organizational principle for continuous integration and interaction of hippocampal memories.

High beta rhythm amplitude in olfactory learning signs a well-consolidated and non-flexible behavioral state.

Beta rhythm (15-30 Hz) is a major candidate underlying long-range communication in the brain. In olfactory tasks, beta activity is strongly modulated by learning but its condition of expression and the network(s) responsible for its generation are unclear. Here we analyzed the emergence of beta activity in local field potentials recorded from olfactory, sensorimotor and limbic structures of rats performing an olfactory task. Rats performed successively simple discrimination, rule transfer, memory recall tests and contingency reversal. Beta rhythm amplitude progressively increased over learning in most recorded areas. Beta amplitude reduced to baseline when new odors were introduced, but remained high during memory recall. Intra-session analysis showed that even expert rats required several trials to reach a good performance level, with beta rhythm amplitude increasing in parallel. Notably, at the beginning of the reversal task, beta amplitude remained high while performance was low and, in all tested animals, beta amplitude decreased before rats were able to learn the new contingencies. Connectivity analysis showed that beta activity was highly coherent between all structures where it was expressed. Overall, our results suggest that beta rhythm is expressed in a highly coherent network when context learning - including both odors and reward - is consolidated and signals behavioral inflexibility.

Significance of sniffing pattern during the acquisition of an olfactory discrimination task.

Active sampling of olfactory environment consists of sniffing in rodents. The importance of sniffing dynamics is well established at the neuronal and behavioral levels. Patterns of sniffing have been shown to be modulated by the physicochemical properties of odorants, particularly concentration and sorption. Sniffing is also heavily impacted by higher processing related to the behavioral context, emotion and attentional demand. However, how the pattern of sniffing evolves over the course of learning of an experimental olfactory conditioning is still poorly understood. We tested this question by monitoring sniffing activity, using a whole-body plethysmograph, on rats performing a two-alternative choice odor discrimination task. We followed sniff variations at different learning stages (naïve, well-trained, expert). We found that during the acquisition of an odor discrimination task, rats acquired a global sniffing pattern, independent of the odor pair used. This pattern consists of a longer sampling duration, a higher sniffing frequency, and a larger amplitude. In parallel, subtle differences of sniffing between the two odors of a pair were also observed. This sniffing behavior was not only associated with a better and faster acquisition of the discrimination task but was also transferred to other odor sets and refined after a long-term pause so as to reduce the sampling duration and maintain a specific sniffing frequency. Our results provide additional arguments that sniffing is a complex sensorimotor act that is strongly affected by olfactory learning.

Sniff adjustment in an odor discrimination task in the rat: analytical or synthetic strategy?

A growing body of evidence suggests that sniffing is not only the mode of delivery for odorant molecules but also contributes to olfactory perception. However, the precise role of sniffing variations remains unknown. The zonation hypothesis suggests that animals use sniffing variations to optimize the deposition of odorant molecules on the most receptive areas of the olfactory epithelium (OE). Sniffing would thus depend on the physicochemical properties of odorants, particularly their sorption. Rojas-Líbano and Kay (2012) tested this hypothesis and showed that rats used different sniff strategies when they had to target a high-sorption (HS) molecule or a low-sorption (LS) molecule in a binary mixture. Which sniffing strategy is used by rats when they are confronted to discrimination between two similarly sorbent odorants remains unanswered. Particularly, is sniffing adjusted independently for each odorant according to its sorption properties (analytical processing), or is sniffing adjusted based on the pairing context (synthetic processing)? We tested these hypotheses on rats performing a two-alternative choice discrimination of odorants with similar sorption properties. We recorded sniffing in a non-invasive manner using whole-body plethysmography during the behavioral task. We found that sniffing variations were not only a matter of odorant sorption properties and that the same odorant was sniffed differently depending on the odor pair in which it was presented. These results suggest that rather than being adjusted analytically, sniffing is instead adjusted synthetically and depends on the pair of odorants presented during the discrimination task. Our results show that sniffing is a specific sensorimotor act that depends on complex synthetic processes.