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Stuart, G. J.

Publications and source records attributed to Stuart, G. J..

6 recordsLinked to original sources

Cell-type specific inhibitory dynamics shape binocular response normalization in visual cortex

Response normalization during sensory processing is a canonical cortical computation thought to emerge from inhibition-stabilized networks (ISNs). A key prediction from ISNs is that inhibition tracks and scales with excitation, leading to sublinear response summation, but which interneuron classes mediate this operation is unclear. Here, we investigate temporal dynamics and response summation in parvalbumin (PV) and somatostatin (SST) interneurons in mouse binocular visual cortex (bV1). We find that both PV and SST interneurons are binocular but exhibit distinct temporal dynamics and summation profiles. Binocular responses in PV interneurons tracked pyramidal neuron responses, exhibiting sublinear summation consistent with ISN models. In contrast, binocular responses SST interneurons exhibited rapid temporal dynamics and linear or supralinear summation, deviating from ISN predictions. While both PV and SST neurons received excitatory drive via interhemispheric callosal input, they exhibited distinct cellular properties, synaptic dynamics and input-output transformations. Biophysically constrained simulations indicated that cellular and synaptic differences alone were insufficient to reproduce the observed response dynamics in vivo during binocular integration, which were better explained by class-specific differences in local inhibitory circuit motifs. Together, our results indicate that heterogeneous, cell-type-specific inhibitory dynamics shape response normalization in bV1, with PV but not SST interneurons having ISN-like properties.

neuroscience↗

Superior Colliculus Neurons Encode and Causally Shape Sensory Decisions

The ability of an organism to attend to, and orient towards, relevant stimuli is critical for survival. In the mammalian brain, a principal brain region performing this function is the superior colliculus (SC). Despite its important role in attention and orienting movements, little is known about the role the SC plays in sensory decisions. Using Neuropixel recording and optogenetic perturbation of neuronal activity in awake behaving mice, we provide a quantitative link between the activity of neurons in the SC and the behavioural outcome during a whisker-dependent sensory detection task. Consistent with the idea that the SC contributes to sensory decision-making, the activity of SC neurons was correlated with behavioural performance. Furthermore, we found that optogenetic inhibition of the SC reduced behavioural performance without reducing sensitivity or reaction time. These findings indicate that the SC both encodes and causally shapes sensory decisions during a whisker-dependent task.

neuroscience↗

Context Shapes Fear: Habituation of Innate Defensive Behaviours Depends on Environmental Context

The capacity of animals to rapidly and appropriately respond to potential threats is critical for survival. In many species, this involves innate defensive behaviours, such as escape or freezing. But not all threats are dangerous. Habituation - a form of non-associative learning - allows animals to filter out irrelevant stimuli and thereby avoid unnecessary energy expenditure. While it is well known that context can influence behavioural responses to associative learning, whether non-associative forms of learning, such as habituation, are also context-dependent is unclear. Here, we address this issue in mice by examining the role of environmental context on habituation of defensive behaviours to threatening visual stimuli. We first developed a protocol leading to rapid (within minutes) and stable (at least one week) habituation of freezing responses to slowly sweeping visual stimuli, resembling an aerial predator moving across the sky. Using this protocol, we tested the impact of environmental context on habituation of freezing responses, finding that changing the environmental context led to a significant and reversible reduction in habituation. In summary, we find that environmental context plays a critical role in determining the impact of habituation on visually evoked innate defensive behaviours. These findings reveal a previously unrecognised flexibility in defensive responses to visual threats, extending the influence of environmental context to non-associative learning. HighlightsO_LIMice freeze in response to sweeping visual stimuli, resembling an aerial predator. C_LIO_LIHabituation to sweeping visual stimuli could be induced rapidly and remained stable over time. C_LIO_LIHabituation to sweeping visual stimuli depended on environmental context. C_LIO_LIContext-specific habituation was reversible. C_LI

animal behavior and cognition↗

Binocular processing facilitates escape behavior through multiple pathways to the superior colliculus

The superior colliculus (SC) is the main brain region regulating innate defensive behaviors to visual threat. Yet, how the SC integrates binocular visual information and to what extent binocular vision drives defensive behaviors is unknown. Here, we show that binocular vision facilitates visually-evoked escape behavior. Furthermore, we find that SC neurons respond to binocular visual input with diverse synaptic and spiking responses, and summate visual inputs largely sublinearly. Using pathway-specific optogenetic silencing we find that contralateral and ipsilateral visual information is carried to binocular SC neurons through retinal, interhemispheric and corticotectal pathways. These pathways carry binocular visual input to the SC in a layer-specific manner, with superficial layers receiving visual information through retinal input, whereas intermediate and deep layers rely on interhemispheric and corticotectal pathways. Together, our data shed light on the cellular and circuit mechanisms underlying binocular visual processing in the SC and its role in escape behavior.

neuroscience↗

Higher synaptic threshold for NMDA spike generation in human neurons

Neurons receive synaptic input primarily onto their dendrites. While we know much about the electrical properties of dendrites in rodents, we have only just started to describe their properties in the human brain. Here we investigate the capacity of human neurons to generate NMDA spikes. We find that dendritic iontophoresis of glutamate, as well as local dendritic synaptic stimulation, can evoke NMDA spikes in dendrites of human layer 2/3 pyramidal neurons. Surprisingly, however, the capacity to evoke NMDA spikes in human neurons was significantly reduced compared to that in rodent neurons. Simulations in morphologically realistic models indicated that human neurons have a higher synaptic threshold for NMDA spike generation. Using a simplified model, we show that this is primarily due to the larger diameter of human dendrites. In summary, we find reduced NMDA spike generation in human compared to rodent neurons due to the larger diameter of human dendrites.

neuroscience↗

Superior colliculus modulates cortical coding of somatosensory information

The cortex sends a direct projection to the superior colliculus. What is largely unknown is whether (and if so how) the superior colliculus modulates activity in the cortex. Here, we directly investigate this issue, showing that optogenetic activation of superior colliculus changes the input-output relationship of neurons in somatosensory cortex during whisker movement, enhancing responses to low amplitude whisker deflections. While there is no direct pathway from superior colliculus to somatosensory cortex, we found that activation of superior colliculus drives spiking in the posterior medial (POm) nucleus of the thalamus via a powerful monosynaptic pathway. Furthermore, POm neurons receiving input from superior colliculus provide excitatory input to somatosensory cortex. Silencing POm abolished the capacity of superior colliculus to modulate cortical whisker responses. Our findings indicate that the superior colliculus, which plays a key role in attention, modulates sensory processing in somatosensory cortex via a powerful disynaptic pathway through the thalamus.

neuroscience↗