Sex Differences in the Ventral Hippocampus to Lateral Septum Pathway in Modulating Social Recognition Memory Public

Abstract

The ability to discriminate between novel and familiar individuals is central to human social life. Deficits in social recognition memory are core symptoms in several neurological diseases such as Alzheimer’s disease and Autism Spectrum Disorder. Despite the debilitating nature of these diseases, the neural circuits underlying social recognition memory remain poorly understood. The ventral hippocampus has been implicated in social recognition memory. The ventral hippocampus, however, projects to several downstream regions including the lateral septum, a region involved in regulating a wide number of behaviors such as aggression, feeding, and kinship behavior. Previous studies performed by our lab have established that the ventral hippocampus to lateral septum pathway modulates social recognition memory in male mice. Yet, it remained unknown whether the pathway plays a similar role in female mice. In this study, we combined intersectional viral strategies, chemogenetics, and histology in rodent models to probe the role of the ventral hippocampus to lateral septum pathway in mediating social recognition memory in female mice. Similar to results seen in male mice, we found that inhibition of the pathway disrupted social recognition memory in female mice, suggesting that the ventral hippocampus to lateral septum circuit regulates social recognition memory in both male and female mice. Future studies that further examine this pathway will shed light on the neural circuits underlying social recognition memory and answer the fundamental question, “How do we recognize each other?”

Table of Contents

Introduction ................................................................................................................................1

Hippocampus Anatomy ................................................................................................................1

Fig 1: A simplified example of the trisynaptic circuit found within the HPC.. ....................................2

Hippocampus Function ................................................................................................................3

Dorsal Hippocampus ....................................................................................................................5

Fig 2: Notable inputs and outputs of the dHPC ...............................................................................6

Ventral Hippocampus ...................................................................................................................6

Fig 3: Notable inputs and outputs of the vHPC ...............................................................................7

Lateral Septum ............................................................................................................................8

Fig 4: Notable inputs and outputs of the LS ................................................................................... 8

Materials and Methods ................................................................................................................11

Subjects ..................................................................................................................................... 11

Stereotaxic Surgery ..................................................................................................................... 11

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) .........................................12

Social Discrimination Task (SDT) ..................................................................................................12

Fig 5: The SDT was performed in four different conditions...............................................................13

Open Field Assay ......................................................................................................................... 13

Histology and Imaging ................................................................................................................. 13

Statistical Analysis .......................................................................................................................14

Results ........................................................................................................................................14

Inhibition of the vHPC-LS pathway disrupted social recognition in both male and female mice ......... 14

Fig 6: Inhibition of the vHPC-LS pathway disrupted social recognition memory. ...............................15

Inhibition did not influence investigation ......................................................................................16

Fig 7: Inhibition of the vHPC-LS pathway did not influence investigation ........................................ 17

Inhibition did not impact preference for objects .............................................................................18

Fig 8: Inhibition did not influence preference for objects .................................................................19

Inhibition and food preference ......................................................................................................19

Fig 9: Inhibition and food preference ............................................................................................. 21

Inhibition of the vHPC-LS pathway is not anxiogenic ...................................................................... 21

Fig 10: Inhibition of the vHPC-LS pathway did not alter anxiety .......................................................23

Discussion ....................................................................................................................................23

Social Recognition Memory ........................................................................................................... 23

Social Investigation and Object Preference ......................................................................................24

Food Preference ............................................................................................................................25

Anxiety and Locomotion ............................................................................................................... 25

Limitations and Future Directions ..................................................................................................26

References Cited ...........................................................................................................................28

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Mot-clé	Sex Differences Memory Lateral Septum Social Recognition Ventral Hippocampus DREADDS DREADDs
Committee Chair / Thesis Advisor	Dr. Malavika Murugan, Emory University
Committee Members	Dr. Joseph Manns, Emory University Dr. Larry Young, Emory University

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