Fig. 7

Fig. 7

Noradrenergic System Signals Visuomotor Mismatch; Radial Astrocytes Accumulate Evidence that Actions Are Futile

(A) Mismatch assay. Left: in closed loop, motor output triggers visual feedback (motosensory gain > 0). Middle: stimulus only with no swimming. Right: sensory-motor mismatch in swim failures (gain = 0).

(B) Mismatch signals in NE-MO. In closed loop or visual signal alone, NE-MO responses were small. During swim failures, NE-MO responses were large. (See Figure S6H for LC, which does not respond to mismatch until next swim bout.)

(C) Extended mismatch assay: motosensory gain randomly set for each swim bout, varying combinations of motor vigor and visual velocity.

(D–G) NE-MO responses encode sensory-motor mismatch. (D and E) NE-MO responses grew with stronger motor vigor if no visual stimulus was shown. (D, example fish; E, population data, 10 fish.) (F and G) NE-MO responses were minimal in closed loop (motosensory gain > 0), whether gain was high or low. In open loop (no feedback, gain = 0) NE-MO responded. With opposite feedback (forward visual feedback during swimming, high mismatch, motosensory gain < 0), NE-MO response was larger. In (F and G), average motor vigor is similar across visual speeds due to randomization of gain. (F, example fish; G, population data, 11 fish). Shading, SEM.

(H) Radial astrocyte Ca²⁺ integrates swim failures. Fish swam in closed loop, then open loop for 1, 2, 4, 8, or 16 swim bouts, then back to closed loop. Glial signals increased with number of failed bouts after ∼2 failed bouts; NE-MO signals began increasing with first failed bout. Trials with passivity not included. NE-MO signal sometimes saturated or decreased while glial Ca²⁺ continued to increase.

(I) Radial astrocyte Ca²⁺ accumulated with increasing numbers of swim failures. NE-MO Ca²⁺ also increased initially but saturated or decreased, while glial Ca²⁺ continued to increase with swim failures until feedback returns to closed loop. Gray arrows, accumulation.

(J) Experiment: information accumulation in radial astrocytes. In a swim bout, probability that fish sees visual feedback (backward visual flow) is P. P = 1, closed loop; P = 0, open loop; intermediate P gives probabilistic feedback.

(K) Information accumulation in radial astrocytes. Ca²⁺ signal, averaged over fish and trials, reflects P, the probability that a swim bout gives visual feedback, so glia accumulate information on swim futility over time (n = 14 fish).

(L) Circuit diagram. NE-MO represents mismatch signal, computed from visual and motor efference input. Noradrenergic axons from NE-MO excite glial processes in L-MO through α1B NE receptors (see Figure S6C for projections). Radial astrocytes integrate mismatch signals and suppress swimming via downstream GABAergic neurons.