Biology subjects

Root, C. M.

Publications and source records attributed to Root, C. M..

3 recordsLinked to original sources

bioRxiv2024

Control of innate olfactory valence by segregated cortical amygdala circuits

Animals exhibit innate behaviors that are stereotyped responses to specific evolutionarily relevant stimuli in the absence of prior learning or experience. These behaviors can be reduced to an axis of valence, whereby specific odors evoke approach or avoidance responses. The posterolateral cortical amygdala (plCoA) mediates innate attraction and aversion to odor. However, little is known about how this brain area gives rise to behaviors of opposing motivational valence. Here, we sought to define the circuit features of plCoA that give rise to innate attraction and aversion to odor. We characterized the physiology, gene expression, and projections of this structure, identifying a divergent, topographic organization that selectively controls innate attraction and avoidance to odor. First, we examined odor-evoked responses in these areas and found sparse encoding of odor identity, but not valence. We next considered a topographic organization and found that optogenetic stimulation of the anterior and posterior domains of plCoA elicits attraction and avoidance, respectively, suggesting a functional axis for valence. Using single cell and spatial RNA sequencing, we identified the molecular cell types in plCoA, revealing an anteroposterior gradient in cell types, whereby anterior glutamatergic neurons preferentially express VGluT2 and posterior neurons express VGluT1. Activation of these respective cell types recapitulates appetitive and aversive behaviors, and chemogenetic inhibition reveals partial necessity for responses to innate appetitive or aversive odors. Finally, we identified topographically organized circuits defined by projections, whereby anterior neurons preferentially project to medial amygdala, and posterior neurons preferentially project to nucleus accumbens, which are respectively sufficient and necessary for innate attraction and aversion. Together, these data advance our understanding of how the olfactory system generates stereotypic, hardwired attraction and avoidance, and supports a model whereby distinct, topographically distributed plCoA populations direct innate olfactory responses by signaling to divergent valence-specific targets, linking upstream olfactory identity to downstream valence behaviors, through a population code. This suggests a novel amygdala circuit motif in which valence encoding is represented not by the firing properties of individual neurons, but by population level identity encoding that is routed through divergent targets to mediate distinct behaviors of opposing appetitive and aversive responses.

neuroscience↗

bioRxiv2023

Transformation of value signaling in a striatopallidal circuit

The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Though we have identified many brain nuclei that play various roles in reward processing, a significant gap remains in understanding how valence encoding transforms through the layers of sensory processing. To address this gap, we carried out a comparative investigation of the anteromedial olfactory tubercle (OT), and the ventral pallidum (VP) - 2 connected nuclei of the basal ganglia which have both been implicated in reward processing. First, using anterograde and retrograde tracing, we show that both D1 and D2 neurons of the anteromedial OT project primarily to the VP and minimally elsewhere. Using 2-photon calcium imaging, we then investigated how the identity of the odor and reward contingency of the odor are differently encoded by neurons in either structure during a classical conditioning paradigm. We find that VP neurons robustly encode reward contingency, but not identity, in low-dimensional space. In contrast, the OT neurons primarily encode odor identity in high-dimensional space. Although D1 OT neurons showed larger responses to rewarded odors than other odors, consistent with prior findings, we interpret this as identity encoding with enhanced contrast. Finally, using a novel conditioning paradigm that decouples reward contingency and licking vigor, we show that both features are encoded by non-overlapping VP neurons. These results provide a novel framework for the striatopallidal circuit in which a high-dimensional encoding of stimulus identity is collapsed onto a low-dimensional encoding of motivational valence.

neuroscience↗

bioRxiv2022

Amygdalostriatal transition zone neurons encode sustained valence to direct conditioned behaviors

To ensure survival, the brain must rapidly identify threats and maintain defensive behaviors for as long as danger is present. The amygdala has been studied as a key site for fear responses, but responses to threat cues in amygdala neurons are largely transient and shorter in duration than defensive responses observed. Here, we present the amygdalostriatal transition zone (ASt) as a missing piece of the circuits mediating fear responses. Using single-nucleus RNA sequencing (snRNA-seq), we demonstrate that the ASt is genetically distinct from adjacent striatal and amygdalar structures. In vivo electrophysiology and calcium imaging reveal that ASt neurons have robust, sustained responses to shock-predicting cues. Further, photostimulation of the ASt is sufficient to drive freezing and avoidance behaviors, and optogenetic inhibition experiments show that Drd2+ ASt neurons are necessary for cue-conditioned fear responses. Our findings establish the ASt as a previously unappreciated yet critical structure for encoding learned associations and directing defensive behaviors.

neuroscience↗