Curtu, R. | Search bioRxiv

bioRxiv2023

Complementary cognitive roles for D2-MSNs and D1-MSNs in interval timing

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2- dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway. We found that D2-MSNs and D1-MSNs exhibited distinct dynamics over temporal intervals as quantified by principal component analyses and trial-by-trial generalized linear models. MSN recordings helped construct and constrain a four-parameter drift-diffusion computational model in which MSN ensemble activity represented the accumulation of temporal evidence. This model predicted that disrupting either D2-MSNs or D1-MSNs would increase interval timing response times and alter MSN firing. In line with this prediction, we found that optogenetic inhibition or pharmacological disruption of either D2-MSNs or D1-MSNs increased interval timing response times. Pharmacologically disrupting D2-MSNs or D1-MSNs also changed MSN dynamics and degraded trial-by-trial temporal decoding. Together, our findings demonstrate that D2-MSNs and D1-MSNs had opposing dynamics yet played complementary cognitive roles, implying that striatal direct and indirect pathways work together to shape temporal control of action. These data provide novel insight into basal ganglia cognitive operations beyond movement and have implications for human striatal diseases and therapies targeting striatal pathways.

neuroscience↗

bioRxiv2020

Buildup and bistability in auditory streaming as an evidence accumulation process with saturation

A repeating triplet-sequence ABA_ of non-overlapping brief tones, A and B, is a valued paradigm for studying auditory stream formation and the cocktail party problem. The stimulus is "heard" either as a galloping pattern (integration) or as two interleaved streams (segregation); the initial percept is typically integration then followed by spontaneous alternations between segregation and integration, each being dominant for a few seconds. The probability of segregation grows over seconds, from near-zero to a steady value, defining the buildup function, BUF. Its stationary level increases with the difference in tone frequencies, DF, and the BUF rises faster. Percept durations have DF -dependent means and are gamma-like distributed. Behavioral and computational studies usually characterize triplet streaming either during alternations or during buildup. Here, our experimental design and modeling encompass both. We propose a pseudo-neuromechanistic model that incorporates spiking activity in primary auditory cortex, A1, as input and resolves perception along two network-layers downstream of A1. Our model is straightforward and intuitive. It describes the noisy accumulation of evidence against the current percept which generates switches when reaching a threshold. Accumulation can saturate either above or below threshold; if below, the switching dynamics resemble noise-induced transitions from an attractor state. Our model accounts quantitatively for three key features of data: the BUFs, mean durations, and normalized dominance duration distributions, at various DF values. It describes perceptual alternations without competition per se, and underscores that treating triplets in the sequence independently and averaging across trials, as implemented in earlier widely cited studies, is inadequate. Author summarySegregation of auditory objects (auditory streaming) is widely studied using ambiguous stimuli. A sequence of repeating triplets ABA_ of non-overlapping brief pure tones, A and B, frequency-separated, is a valued stimulus. Studies typically focus on one of two behavioral phases: the early (say, ten seconds) buildup of segregation from the default integration or later spontaneous alternations (bistability) between seconds-long integration and segregation percepts. Our experiments and modeling encompass both. Our novel, data-driven, evidence-accumulation model accounts for key features of the observations, taking as input recorded spiking activity from primary auditory cortex (as opposed to most existing, more abstract, models). Our results underscore that assessing individual triplets independently and averaging across trials, as in some earlier studies, is inadequate (lacking neuronal-accountability for percept duration statistics, the underlying basis of buildup). Further, we identify fresh parallels between evidence accumulation and competition as potential dynamic processes for choice in the brain.

neuroscience↗