Arie Kaffman, MD, PhD

Associate Professor of Psychiatry

Other Departments & Organizations

• Microglia Cells Are Highly Sensitive to Impoverished Conditions Early in Life

  Microglia from normally developing mouse brain are large highly ramified cells containing large number of synaptic puncta (red dots), Indicating efficient removal of non-functional synapses in the developing hippocampus. In contrast, mice exposed to early life adversity are smaller and contain fewer synaptic puncta. For more details, see Dayanada et.al. 2023, DOI: 10.1016/j.bbi.2022.09.014.

• Working Model

  (A) The number of microglia and their size increases from P12-21 in the hippocampus. During this critical period, expression of TREM2 on microglia increases allowing for efficient removal of non-functional synapses labeled with “eat me signals”. This process ensures the formation of more efficient network characterized by high maturity index and is necessary for normal hippocampal function. (B) Exposure to LB reduces TREM2 expression and impairs synaptic pruning during the 2^nd and third weeks of life. (C) As a result, adolescent LB mice have reduced maturity index calculated as the ratio between mature mushroom spines (green) and immature spines such as stubby, thin and filopodia (purple, blue, red). For more details, see Dayanada et.al. 2023, DOI: 10.1016/j.bbi.2022.09.014.

• UPS increases anxiety-like behavior in males

  In this study we show that exposure to unpredictable complex stress early in life (UPS) causes more significant anxiety-like behavior compared to the predictable and less severe stress limited bedding or LB. Further, the anxiety behavior is more pronounced in males compared to females. For more details see Johnson et al 2018 doi: 10.1038/s41398-018-0092-z.
• UPS causes structural changes that resemble those seen in humans exposed to early adversity

  Unpredictable postnatal stress (UPS) causes volumetric and fractional anisotropy changes that resemble those reported in humans and were seen in both males and females. Interestingly, UPS causes sex specific in fronto-limbic connectivity and microglial function in males and females. For more details see White et al. 2020, doi: 10.7554/eLife.58301
• Limited Bedding Impairs Perforant Pathway Connectivity in Male but not Female Adolescent Mice

  Reelin-positive cells project from the lateral entorhinal cortex (LEC) to the dorsal hippocampus via the perforant pathway. These connections are essential for normal hippocampal dependent memory and development. We recently found that these projections fail to form in adolescent male, but not female mice exposed to limited bedding (LB). For additional details see https://www.biorxiv.org/content/10.1101/2023.08.08.552517v1.

• The Kaffman Lab