Abstract |
Until recently, neuroscience research focused on the anatomical, physiological, and functional
properties of individual neurons. However, neurons do not work in isolation: they work together in
neuronal circuits. Understanding brain-wide neuronal communication through specific patterns of
long-range synaptic connectivity is a step closer to understanding cognition, behavior and emotion,
and how these get impaired in neuropsychiatric disorders. The prefrontal cortex (PFC) is the so-called
"executive center" of the brain involved in high-level cognitive functions, emotion, attention and
perception. Impairments of the PFC are implicated in diverse neuropsychiatric disorders, including
schizophrenia, attention deficit hyperactivity disorder (ADHD), addiction, and depression. Wholebrain connectivity studies have shown that the mouse PFC has extensive connections to nearly all
brain areas; it receives a variety of long-range excitatory inputs and sends diverse outputs (Gao et al.,
2022, Anastasiades & Carter, 2021). Additionally, adaptations in synaptic activity and connectivity
during development are critical to proper circuit wiring, and synaptic impairments during
development can lead to circuit dysfunction and disorders. Therefore, studying neuronal circuits in
different developmental levels is essential for understanding the formation of circuits and their role
in cognitive functions and emotional behavior. Here, we combined circuit-tracing approaches and
whole-cell patch clamp recordings to study the intrinsic excitation and inhibition properties of a single
neuronal population (L2/3 pyramidal neurons of the mouse PFC) projecting to two distinct brain
areas: the contralateral PFC hemisphere (cPFC) or the amygdala (AMY). We choose these two
projections as they are involved in PFC-mediated cognitive functions and emotional regulation,
respectively. To dissect the cortico-cortical and cortico-amygdalar neurons, a retrograde fluorescent
substance (cholera toxin B) was stereotaxically injected into the PFC or AMY of mice at different
developmental stages (adolescent, adult). Whole-cell patch clamp recordings of the projecting PFC
neurons revealed a significant effect of the developmental stage on the spontaneous excitatory
postsynaptic current (sEPSC) frequency of cortico-amygdalar projections. An overall tendency of
higher excitation/inhibition (E/I) ratio was observed in adult compared to adolescent mice, in both
circuits. Overall, this study provides useful insights in the cortico-cortical (PFC→cPFC) and corticoamygdalar (PFC→BLA) projections of L2/3 pyramidal neurons of the prelimbic area of the prefrontal
cortex, across development and in both sexes.
|