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

Abstract

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.

Quantitative analysis of rabies virus-based synaptic connectivity tracing

“…In addition, various methods are used to analyze rabies tracing experiments. Metrics used in previous studies include input fraction (the inputs count per area relative to either the total number of input cells in the brain, sometimes referred to as total input fraction, [18,19,15,20,21],…”

“…In addition, various methods are used to analyze rabies tracing experiments. Metrics used in previous studies include input fraction (the inputs count per area relative to either the total number of input cells in the brain, sometimes referred to as total input fraction,[18, 19, 15, 20, 21], or relative to the number of input cells in a given area [15, 22] or layer [23]), and the convergence index, also called input connection strength index or input magnitude (area inputs count normalized by number of starter cells [24, 25, 18, 20, 26]). The disparity in methods and terminology used to report the properties of connectivity maps complicates direct comparisons across various studies.…”