Biology subjects

Goldbach, H. C.

Publications and source records attributed to Goldbach, H. C..

5 recordsLinked to original sources

bioRxiv2025

Cholinergic-dependent dopamine signals in mouse dorsal striatum are regulated by frontal but not sensory cortices

Everyday decisions depend on linking sensory stimuli with actions and outcomes. The striatum supports these sensorimotor associations through dopamine-dependent plasticity. Thus, the timing and magnitude of dopamine release is critical for learning. Recent work has characterized a local striatal microcircuit in which cholinergic interneurons (CINs) modulate dopamine release via acetylcholine activation of nicotinic receptors on dopamine axons. Here, we show that visual stimuli evoke dopamine responses in the dorsomedial striatum through this cholinergic-dependent mechanism. Using anatomical and functional methods to identify which pathways elicit these signals, we found that visual and auditory cortices that project to the dorsomedial striatum lack robust connectivity to CINs and were unable to drive cholinergic-dependent dopamine release. In contrast, frontal cortical regions, including the prelimbic and anterior cingulate cortices, strongly recruited CINs and acetylcholine, producing robust dopamine release both ex vivo and in vivo. These frontal corticostriatal projections are activated by visual stimuli, representing a possible pathway by which visual information reaches the dorsomedial striatum to evoke dopamine. These findings reveal a fundamental distinction between sensory and frontal cortical inputs to the striatum, demonstrating that only the latter evoke cholinergic-dependent dopamine signaling. This work establishes a framework for understanding how cortical circuits shape striatal dopamine to support reinforcement learning.

neuroscience↗

bioRxiv2025

A synaptic mechanism for encoding the learned value of action-derived safety

Motivated behavior is often framed in terms of biologically grounded outcomes, such as food or threat. Yet many motivated actions, like the pursuit of safety or agency, depend on outcomes that lack explicit sensory value and must instead be inferred from experience. Here, we identify a thalamostriatal circuit mechanism by which such internally constructed outcomes acquire motivational value. In mice performing an active avoidance task, neurons in the paraventricular thalamus (PVT) projecting to the nucleus accumbens (NAc) develop a safety-encoding signal that emerges following successful avoidance. This signal is experience-dependent and value-sensitive, diminishing upon devaluation of the instrumental contingency. Selective silencing of the PVT[->]NAc projection at safety onset disrupts avoidance persistence without impairing action-outcome learning, as confirmed by computational modeling of value updating based on prediction error. Mechanistically, PVT input recruits cholinergic interneurons (CINs) to modulate dopamine release and this influence depends on synaptic potentiation mediated by GluA2-lacking AMPA receptor insertion at PVT-CIN synapses. Disrupting this plasticity selectively impairs the avoidance response by blunting the motivational value of safety without affecting acquisition. These findings reveal how thalamic circuits assign value to abstract, internal outcomes, providing a framework for understanding how goals like safety are inferred, stabilized, and rendered behaviorally effective.

neuroscience↗

bioRxiv2022

Excitation creates a distributed pattern of cortical suppression due to varied recurrent input

Dense local, recurrent connections are a major feature of cortical circuits, yet how they affect neurons responses is unclear, with some studies reporting weak recurrent effects, some amplification, and others showing instead local suppression. Here, we show that optogenetic input to mouse V1 excitatory neurons generates salt-and-pepper patterns of both excitation and suppression. Responses in individual neurons are not strongly predicted by that neurons direct input. A balanced-state network model reconciles a set of diverse observations: the observed dynamics, suppressed responses, decoupling of input and output, and long tail of excited responses. The model shows recurrent excitatory-excitatory connections are strong and also variable across neurons. Together, these results demonstrate that excitatory recurrent connections can have major effects on cortical computations, by shaping and changing neurons responses to input.

neuroscience↗

bioRxiv2020

Performance in even a simple perceptual task depends on mouse secondary visual areas

Primary visual cortex (V1) in the mouse projects to numerous brain areas, including several secondary visual areas, frontal cortex, and basal ganglia. While it has been demonstrated that optogenetic silencing of V1 strongly impairs visually-guided behavior, it is not known which downstream areas are required for visual behaviors. Here we trained mice to perform a contrast-increment change detection task, for which substantial stimulus information is present in V1. Optogenetic silencing of visual responses in secondary visual areas revealed that their activity is required for even this simple visual task. In vivo electrophysiology showed that, although inhibiting secondary visual areas could produce some feedback effects in V1, the principal effect was profound suppression at the location of the optogenetic light. The results show that pathways through secondary visual areas are necessary for even simple visual behaviors.

neuroscience↗

bioRxiv2019

Inhibition stabilization is a widespread property of cortical networks

Many cortical network models use recurrent coupling strong enough to require inhibition for stabilization. Yet it has been experimentally unclear whether inhibition-stabilized network (ISN) models describe cortical function well across areas and states. Here we test several ISN predictions, including the counterintuitive (paradoxical) suppression of inhibitory firing in response to optogenetic inhibitory stimulation. We find clear evidence for ISN operation in mouse visual, somatosensory, and motor cortex. Simple two-population ISN models describe the data well and let us quantify coupling strength. Though some models predict a non-ISN to ISN transition with increasingly strong sensory stimuli, we find ISN effects without sensory stimulation and even during light anesthesia. Additionally, average paradoxical effects result only with transgenic, not viral, opsin expression in parvalbumin (PV)-positive neurons; theory and expression data show this is consistent with ISN operation. Taken together, these results show strong coupling and inhibition stabilization are common features of cortex.

neuroscience↗