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The medial prefrontal cortex (mPFC) is critically involved in cognitive and emotional function and underlies many neuropsychiatric disorders, including mood, fear and anxiety disorders. In rodents, disruption of mPFC activity affects anxiety- and depression-like behavior, with evidence supporting specialized contributions from its subdivisions. The rodent mPFC is often subdivided into the anterior cingular cortex (ACC), prelimbic cortex (PL), and the infralimbic cortex (IL), and broken down into the dorsomedial prefrontal cortex (dmPFC), spanning ACC and dorsal PL, and the ventromedial prefrontal cortex (vmPFC), which includes the ventral PL, IL, and in some studies the dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT). The DP/DTT have recently been implicated in the regulation of stress-induced sympathetic responses via projections to the hypothalamus. While many studies implicate the PL and IL in anxiety-, depression-like and fear behavior, the contribution of the DP/DTT to affective and emotional behavior remains unknown. Here, we used chemogenetics to bidirectionally modulate DP/DTT activity and examine its effects on affective behaviors, cognition and stress responses in naïve male and female C57BL/6J mice. We found that acute chemogenetic activation of DP/DTT neurons caused a significant increase in anxiety-like behavior in the open field and elevated plus maze tests, as well as in passive coping in the tail suspension test. In contrast, chemogenetic inhibition of the DP/DTT had no effect on affective behavior, but facilitated auditory fear memory acquisition without affecting memory retrieval. Additionally, DP/DTT activation led to an increase in plasma corticosterone levels. These findings point to the DP/DTT as a new regulator of affective behavior in mice.

The ability to generate memories that persist throughout a lifetime (that is, memory persistence) emerges in early development across species. Although it has been shown that persistent fear memories emerge between late infancy and adolescence in mice, it is unclear exactly when this transition takes place, and whether two major fear conditioning tasks, contextual and auditory fear, share the same time line of developmental onset. Here, we compared the ontogeny of remote contextual and auditory fear in C57BL/6J mice across early life. Mice at postnatal day (P)15, 21, 25, 28, and 30 underwent either contextual or auditory fear training and were tested for fear retrieval 1 or 30 d later. We found that mice displayed 30-d memory for context– and tone–fear starting at P25. We did not find sex differences in the ontogeny of either type of fear memory. Furthermore, 30-d contextual fear retrieval led to an increase in the number of c-Fos positive cells in the prelimbic region of the prefrontal cortex only at an age in which the contextual fear memory was successfully retrieved. These data delineate a precise time line for the emergence of persistent contextual and auditory fear memories in mice and suggest that the prelimbic cortex is only recruited for remote memory recall upon the onset of memory persistence.

Spontaneous recognition memory tasks build on an animal’s natural preference for novelty to assess the what, where and when components of episodic memory. Their simplicity, ethological relevance and cross-species adaptability make them extremely useful to study the physiology and pathology of memory. Recognition memory deficits are common in rodent models of neurodevelopmental disorders, and yet very little is known about the expression of spontaneous recognition memory in young rodents. This is exacerbated by the paucity of data on the developmental onset of recognition memory in mice, a major animal model of disease. To address this, we characterized the ontogeny of three types of spontaneous recognition memory in mice: object location, novel object recognition and temporal order recognition. We found that object location is the first to emerge, at postnatal day (P)21. This was followed by novel object recognition (24 h delay), at P25. Temporal order recognition was the last to emerge, at P28. Elucidating the developmental expression of recognition memory in mice is critical to improving our understanding of the ontogeny of episodic memory, and establishes a necessary blueprint to apply these tasks to probe cognitive deficits at clinically relevant time points in animal models of developmental disorders.

Spontaneous recognition memory tasks explore thewhat,whereandwhencomponents of recognition memory. These tasks are widely used in rodents to assess cognitive function across the lifespan. While several neurodevelopmental and mental disorders present symptom onset in early life, very little is known about how memories are expressed in early life, and as a consequence how they may be affected in pathological conditions. In this review, we conduct an analysis of the studies examining the expression of spontaneous recognition memory in young rodents. We compiled studies using four different tasks: novel object recognition, object location, temporal order recognition and object place. First, we identify major sources of variability between early life spontaneous recognition studies and classify them for later comparison. Second, we use these classifications to explore the current knowledge on the ontogeny of each of these four spontaneous recognition memory tasks. We conclude by discussing the possible implications of the relative time of onset for each of these tasks and their respective neural correlates. In compiling this research, we hope to advance on establishing a developmental timeline for the emergence of distinct components of recognition memory, while also identifying key areas of focus for future research. Establishing the ontogenetic profile of rodent spontaneous recognition memory tasks will create a necessary blueprint for cognitive assessment in animal models of neurodevelopmental and mental disorders, a first step towards improved and earlier diagnosis as well as novel intervention strategies.