Biology subjects

Bloss, E. B.

Publications and source records attributed to Bloss, E. B..

4 recordsLinked to original sources

bioRxiv2026

Sex-specific plasticity mechanisms mediating fear extinction

Strong evidence suggests synaptic plasticity is the critical cellular mechanism underlying learning and memory. Although the forms of synaptic plasticity used by different circuits vary, a widespread presumption is that the male and female brain has evolved to use the same form of plasticity within the same circuits during learning. We used complimentary approaches to determine how synaptic plasticity within the mouse frontal cortex supports extinction of associative memories. Here, we show that both male and female mice have similar ensemble dynamics in excitatory infralimbic cortical neurons during learning. However, activity in amygdala-projecting neurons was required for extinction memories only in male mice. Likewise, only male mice showed evidence for structural synaptic remodeling and clustering of dendritic spines on infralimbic-amygdala projection neurons. Projection-specific deletion of the glutamate receptor subunit GRIN2B blocked synaptic plasticity and impaired extinction memory in male but not female mice. These distinct mechanisms could be leveraged for precise therapies for mental health conditions relative to the present one-size-fits-all approach.

neuroscience↗

bioRxiv2023

Genetic context drives age-related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits

The disconnection of neuronal circuits through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through synaptic structural mechanisms remains unknown. Previous work using rodent and primate models leveraged various techniques to suggest that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus. Here, we examined the effect of aging on synapses on projection neurons forming a hippocampal-cortico-thalamic circuit important for spatial working memory tasks from two genetically distinct mouse strains that exhibit susceptibility (C57BL/6J) or resistance (PWK/PhJ) to cognitive decline during aging. Across both strains, synapses on the CA1-to-PFC projection neurons appeared completely intact with age. In contrast, we found synapse loss on PFC-to-nucleus reuniens (RE) projection neurons from aged C57BL/6J but not PWK/PhJ mice. Moreover, synapses from aged PWK/PhJ mice but not from C57BL/6J exhibited morphological changes that suggest increased synaptic efficiency to depolarize the parent dendrite. Our findings suggest resistance to age-related cognitive decline results in part by age-related synaptic adaptations, and identification of these mechanisms in PWK/PhJ mice could uncover new therapeutic targets for promoting successful cognitive aging and extending human health span.

neuroscience↗

bioRxiv2023

Genetic context controls early microglia-synaptic interactions in mouse models of Alzheimers disease

Common features of Alzheimers disease (AD) include amyloid pathology, microglia activation and synaptic dysfunction, however, the causal relationships amongst them remains unclear. Further, human data suggest susceptibility and resilience to AD neuropathology is controlled by genetic context, a factor underexplored in mouse models. To this end, we leveraged viral strategies to label an AD-vulnerable neuronal circuit in CA1 dendrites projecting to the frontal cortex in genetically diverse C57BL/6J (B6) and PWK/PhJ (PWK) APP/PS1 mouse strains and used PLX5622 to non-invasively deplete brain microglia. Reconstructions of labeled neurons revealed microglia-dependent changes in dendritic spine density and morphology in B6 wild-type (WT) and APP/PS1 yet a marked stability of spines across PWK mice. We further showed that synaptic changes depend on direct microglia-dendrite interactions in B6.APP/PS1 but not PWK.APP/PS1 mice. Collectively, these results demonstrate that microglia-dependent synaptic alterations in a specific AD-vulnerable projection pathway are differentially controlled by genetic context.

neuroscience↗

bioRxiv2021

Hippocampal and thalamic afferents form distinct synaptic microcircuits in the mouse frontal cortex

Neural circuits within the frontal cortex support the flexible selection of goal-directed behaviors by integrating input from brain regions associated with sensory, emotional, episodic, and semantic memory functions. From a connectomics perspective, determining how these disparate afferent inputs target their synapses to specific cell types in the frontal cortex may prove crucial in understanding circuit-level information processing. Here, we used monosynaptic retrograde rabies mapping to examine the distribution of afferent neurons targeting four distinct classes of local inhibitory interneurons and four distinct classes of excitatory projection neurons in mouse infralimbic cortex. Interneurons expressing parvalbumin, somatostatin, or vasoactive intestinal peptide received a large proportion of inputs from hippocampal regions, while interneurons expressing neuron-derived neurotrophic factor received a large proportion of inputs from thalamic regions. A more moderate hippocampal-thalamic dichotomy was found among the inputs targeting excitatory neurons that project to the basolateral amygdala, lateral entorhinal cortex, nucleus reuniens of the thalamus, and the periaqueductal gray. Together, these results show a prominent bias among hippocampal and thalamic afferent systems in their targeting to genetically or anatomically defined sets of frontal cortical neurons. Moreover, they suggest the presence of two distinct local microcircuits that control how different inputs govern frontal cortical information processing.

neuroscience↗