Biology subjects

Cruz-Sanchez, A.

Publications and source records attributed to Cruz-Sanchez, A..

3 recordsLinked to original sources

bioRxiv2025

Maturation of Hippocampus-Medial Prefrontal Cortex Projections Defines a Pathway-Specific Sensitive Period for Cognitive Flexibility

The septotemporal axis of the hippocampus separates it into domains with unique molecular, cellular, downstream connectivity and behavioral profiles, and yet very little is known about the ontogenesis of these highly specialized subcircuits. Here, we used viral tracing, optogenetic-assisted patch clamping, chemogenetics and behavior in mice to examine changes in domain-defined hippocampus efferent projections from postnatal day (P)10 to P60. We found distinct anatomical and synaptic developmental signatures in ventral and intermediate CA1 downstream connectivity, with unique contributions to the prelimbic and infralimbic subregions of the medial prefrontal cortex (mPFC). Juvenile inhibition of the ventral and intermediate CA1-mPFC pathways led to opposing modulation of adult cognitive flexibility, establishing a sex- and pathway-specific sensitive period preceding the stabilization of CA1-mPFC synaptic transmission. Our data elucidate domain- and target-defined postnatal maturation of hippocampus efferents, identifying juvenility as a CA1-mPFC sensitive period with crucial implications for early life influences on adult cognition.

neuroscience↗

bioRxiv2023

Intermediate CA1 is Required for Object-in-Place Recognition Memory in Mice

Many behaviors that are essential for survival, such as retrieving food, finding shelter and locating predator cues, rely on forming effective associations between the identity and location of spatial elements. This identity-location association is commonly assessed in rodents using spontaneous object-in-place (OiP) recognition memory tasks. OiP recognition memory deficits are seen in autism spectrum disorder, schizophrenia, and are used to detect early onset of Alzheimers disease. These deficits are replicated in animal models of neurodevelopmental, neurodegenerative and chromosomal disorders. Mouse models have been widely adopted in behavioral and systems neuroscience research for their ease of genetic manipulations, and yet very few studies have successfully assessed OiP recognition memory or its neural correlates in mice. To address this limitation, we first established that adult C57/129J and C57BL/6J male and female mice are able to successfully perform the two-object, but not the four-object version of the spontaneous OiP recognition task, with retention intervals of five minutes and one hour. Next, using chemogenetic inhibition, we found that two-object OiP requires the activity of the intermediate CA1 (iCA1) subregion of the hippocampus, but not the medial prefrontal cortex or iCA1-medial prefrontal cortex connections. Our data identify hippocampal subregion specialization in the successful assessment of OiP recognition memory in mice, expanding our understanding of the neural basis of spatial memory processing. Significance StatementAssociations between the identity and location of spatial elements (what-where associations), underlie essential behaviours such as finding food, locating shelter and safely navigating the environment. Deficits in identity-location processing occur in patients with neurodevelopmental and neurodegenerative disorders, and are replicated in rodent models using object-in-place (OiP) recognition tasks. While mice have emerged as a widely used animal model to study the biological mechanisms underlying these disorders, nothing is known about the neural substrates of OiP memory in mice. Here we have established and validated a robust experimental paradigm to assess OiP memory in mice, uncovering a specialized contribution of the hippocampal subregion intermediate CA1 to OiP performance and deepening our understanding of the neural signatures of spatial memory processing.

neuroscience↗

bioRxiv2023

Dorsal peduncular cortex activity modulates affective behaviors in mice

The medial prefrontal cortex (mPFC) is critical to 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 specialized contributions from its subdivisions. The rodent mPFC is divided into the dorsomedial prefrontal cortex (dmPFC), spanning the anterior cingulate cortex (ACC) and dorsal prelimbic cortex (PL), and the ventromedial prefrontal cortex (vmPFC), which includes the ventral PL, infralimbic cortex (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 and optogenetics to bidirectionally modulate DP/DTT activity and examine its effects on affective behaviors, fear and stress responses in C57BL/6J mice. Acute chemogenetic activation of DP/DTT significantly increased anxiety-like behavior in the open field and elevated plus maze tests, as well as passive coping in the tail suspension test. DP/DTT activation also led to an increase in serum corticosterone levels and facilitated auditory fear extinction learning and retrieval. Activation of DP/DTT projections to the dorsomedial hypothalamus (DMH) acutely decreased freezing at baseline and during extinction learning, but did not alter affective behavior. These findings point to the DP/DTT as a new regulator of affective behavior and fear extinction in mice.

neuroscience↗