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Krauzlis, R. J.

Publications and source records attributed to Krauzlis, R. J..

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Visual activity in primate superior colliculus requires geniculostriate input

The superior colliculus (SC) is an ancient visual structure whose principle source of visual drive comes directly from the retina. In primates, however, the SC also receives geniculostriate input from primary visual cortex (V1) via the lateral geniculate nucleus (LGN), making it unclear which pathway normally drives visually evoked spiking. Here we tested whether visually evoked spiking in the primate SC depends on retinal signals routed through LGN and V1, rather than on direct retinal input alone. We recorded from macaque SC neurons before and during reversible inactivation of the ipsilateral LGN and found that LGN inactivation nearly abolished visually evoked spiking. This loss was not due to nonspecific suppression of SC, because saccade-related bursts were spared and was observed across SC layers. Magnocellular-biased stimuli, designed to reveal any potential direct retinal drive, failed to produce visually evoked spiking during LGN inactivation. Interhemispheric inhibition (i.e., a "Sprague effect") was ruled out, because contralateral SC silencing during LGN inactivation did not restore SC visual responses. Consistent with a geniculostriate input route to SC, V1 inactivation also reduced SC visual responses, with effects proportional to the overlap between the V1-induced scotoma and the stimulus representation. Together, these results show that visually evoked neural responses in primate SC depend on retinal signals routed through LGN and V1, and that direct retinotectal input is insufficient to drive SC spiking in the absence of geniculostriate input. These findings revise current models of visual drive to the primate SC and constrain theories of SC-dependent visual behavior. HighlightsO_LILGN inactivation nearly eliminates visual but spares movement-related activity in primate SC C_LIO_LINo retinotectal input is detected, even with magnocellular-biased stimuli or in SC input layers C_LIO_LIThe elimination of visual activity cannot be explained by interhemispheric inhibition C_LIO_LIDirect retinal projections are not sufficient to drive visual responses in primate SC C_LI

neuroscience↗

Beyond the Brake: the Subthalamic Nucleus Predominantly Facilitates Action in Non-human Primates

The subthalamic nucleus (STN) is a core component of the basal ganglia circuitry, traditionally viewed as a "brake" that suppresses motor output via the indirect and hyperdirect pathways. While this model explains certain aspects of motor control, it fails to account for the complex involvement of the STN in dynamic, value-based behaviors. Movement-related increases in STN neuronal activity have been well documented across species, but the functional organization of these responses during value-based decisions has remained unclear. Here, we recorded 187 STN neurons from macaque monkeys performing a value-based sequential choice task. Data-driven clustering identified three functionally distinct populations. Two populations (comprising approximately 89% of task-responsive neurons) exhibited facilitative activity modulated by learned object value. Temporal alignment analysis revealed that the majority of these neurons were target-locked, suggesting a predominantly stimulus-driven evaluation signal rather than a strictly movement-locked command. A third, smaller population encoded a negative value signal upon presentation of unrewarded objects, independent of subsequent motor strategy. Response latencies of the facilitative STN populations systematically preceded those of functionally analogous populations in the GPe recorded during the same task paradigm, supporting an STN-GPe facilitative pathway for value-based action selection. These findings reveal a functional organization within the ventral STN in which evaluation of stimulus target value, beyond the traditional motor suppressive model, is the predominant mode of processing.

neuroscience↗

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↗

A distinct circuit for biasing visual perceptual decisions and modulating superior colliculus activity through the mouse posterior striatum

The basal ganglia play a key role in visual perceptual decisions. Despite being the primary target in the basal ganglia for inputs from the visual cortex, the posterior striatums (PS) involvement in visual perceptual behavior remains unknown in rodents. We reveal that the PS direct pathway is largely segregated from the dorsomedial striatum (DMS) direct pathway, the other major striatal target for visual cortex. We investigated the role of the PS in visual perceptual decisions by optogenetically stimulating striatal medium spiny neurons in the direct pathway (D1-MSNs) of mice performing a visual change-detection task. PS D1-MSN activation robustly biased visual decisions in a manner dependent on visual context, timing, and reward expectation. We examined the effects of PS and DMS direct pathway activation on neuronal activity in the superior colliculus (SC), a major output target of the basal ganglia. Activation of either direct pathway rapidly modulated SC neurons, but mostly targeted different SC neurons and had opposite effects. These results demonstrate that the PS in rodents provides an important route for controlling visual decisions, in parallel with the better known DMS, and with distinct anatomical and functional properties. Significance StatementThe rodent posterior striatum (PS) is strongly innervated by visual cortex and thalamus, but its functional role in visual behavior has not been explored. We show that the PS initiates a direct pathway through the basal ganglia that is anatomically distinct from the more commonly studied dorsomedial striatum (DMS). Activating the PS direct pathway selectively biases decisions for expected, valued visual events. We also show that both DMS and PS direct pathways modulate neuronal activity in the superior colliculus, a structure critical for visual processing and sensorimotor function, and preferentially modulate collicular units with properties relevant in the visual detection task. These findings identify a distinct and novel circuit through the basal ganglia for controlling visually guided perceptual decisions.

neuroscience↗

Short-latency preference for faces in the primate superior colliculus

Face processing is fundamental to primates and has been extensively studied in higher-order visual cortex. Here we report that visual neurons in the midbrain superior colliculus (SC) display a preference for faces, that the preference emerges within 50ms of stimulus onset - well before "face patches" in visual cortex - and that this activity can distinguish faces from other visual objects with accuracies of [~]80%. This short-latency preference in SC depends on signals routed through early visual cortex, because inactivating the lateral geniculate nucleus, the key relay from retina to cortex, virtually eliminates visual responses in SC, including face-related activity. These results reveal an unexpected circuit in the primate visual system for rapidly detecting faces in the periphery, complementing the higher-order areas needed for recognizing individual faces. One-Sentence SummaryAn unexpected circuit through the primate midbrain reports the presence of a face in peripheral vision in 1/20th of a second.

neuroscience↗

Correlated variability in primate superior colliculus depends on functional class

Correlated variability (spike count correlations, rSC) in a population of neurons can constrain how information is read out, depending on behavioral task and neuronal tuning. Here we tested whether rSC also depends on neuronal functional class. We recorded from populations of neurons in macaque superior colliculus (SC), a structure that contains well-defined functional classes. We found that during a guided saccade task, different classes of neurons exhibited differing degrees of rSC. "Delay class" neurons displayed the highest rSC, especially during the delay epoch of saccade tasks that relied on working memory. This was only present among Delay class neurons within the same hemisphere. The dependence of rSC on functional class indicates that subpopulations of SC neurons occupy distinct circuit niches with distinct inputs. Such subpopulations should be accounted for differentially when attempting to model or infer population coding principles in the SC, or elsewhere in the primate brain.

neuroscience↗

Microsaccades as a marker not a cause for attention-related modulation

Recent evidence suggests that microsaccades are causally linked to the attention-related modulation of neurons - specifically, that microsaccades towards the attended location are required for the subsequent changes in firing rate. These findings have raised questions about whether attention-related modulation is due to different states of attention as traditionally assumed or might instead be a secondary effect of microsaccades. Here, in two rhesus macaques, we tested the relationship between microsaccades and attention-related modulation in the superior colliculus, a brain structure crucial for allocating attention. We found that attention-related modulation emerged even in the absence of microsaccades, was already present prior to microsaccades towards the cued stimulus, and persisted through the suppression of activity that accompanied all microsaccades. Nonetheless, consistent with previous findings, we also found significant attention-related modulation when microsaccades were directed towards, rather than away from, the cued location. Thus, in contrast to the prevailing hypothesis, microsaccades are not necessary for attention-related modulation, at least not in the superior colliculus. They do, however, provide an additional marker for the state of attention, especially at times when attention is shifting from one location to another.

neuroscience↗

Neuronal modulation in the mouse superior colliculus during covert visual selective attention

Covert visual attention is accomplished by a cascade of mechanisms distributed across multiple brain regions. Recent studies in primates suggest a parcellation in which visual cortex is associated with enhanced representations of relevant stimuli, whereas subcortical circuits are associated with selection of visual targets and suppression of distractors. Here we identified how neuronal activity in the superior colliculus (SC) of head-fixed mice is modulated during covert visual attention. We found that spatial cues modulated both firing rate and spike-count correlations, and that the cue-related modulation in firing rate was due to enhancement of activity at the cued spatial location rather than suppression at the uncued location. This modulation improved the neuronal discriminability of visual-change-evoked activity between contralateral and ipsilateral SC neurons. Together, our findings indicate that neurons in the mouse SC contribute to covert visual selective attention by biasing processing in favor of locations expected to contain relevant information.

neuroscience↗

Attention-related modulation of caudate neurons depends on superior colliculus activity

Recent work has implicated the basal ganglia in visual perception and attention, in addition to their traditional role in motor control. The basal ganglia, especially the caudate nucleus "head" (CDh) of the striatum, receive indirect anatomical connections from the superior colliculus, a midbrain structure that is known to play a crucial role in the control of visual attention. To test the possible functional relationship between these subcortical structures, we recorded CDh neuronal activity before and during unilateral SC inactivation in a spatial attention task. SC inactivation significantly altered the attention-related modulation of CDh neurons and strongly impaired the classification of task epochs based on CDh activity. Only inactivation of the same-side of SC as recorded CDh neurons, not the opposite-side, had these effects. These results demonstrate a novel interaction between SC activity and attention-related visual processing in the basal ganglia.

neuroscience↗

Midbrain activity supports high-level visual properties in primate temporal cortex

The evolution of the primate brain is marked by a dramatic increase in the number of neocortical areas that process visual information 1. This cortical expansion supports two hallmarks of high-level primate vision - the ability to selectively attend to particular visual features 2 and the ability to recognize a seemingly limitless number of complex visual objects 3. Given their prominent roles in high-level vision for primates, it is commonly assumed that these cortical processes supersede the earlier versions of these functions accomplished by the evolutionarily older brain structures that lie beneath the cortex. Contrary to this view, here we show that the superior colliculus (SC), a midbrain structure conserved across all vertebrates 4, is necessary for the normal expression of attention-related modulation and object selectivity in a newly identified region of macaque temporal cortex. Using a combination of psychophysics, causal perturbations and fMRI, we identified a localized region in the temporal cortex that is functionally dependent on the SC. Targeted electrophysiological recordings in this cortical region revealed neurons with strong attention-related modulation that was markedly reduced during attention deficits caused by SC inactivation. Many of these neurons also exhibited selectivity for particular visual objects, and this selectivity was also reduced during SC inactivation. Thus, the SC exerts a causal influence on high-level visual processing in cortex at a surprisingly late stage where attention and object selectivity converge, perhaps determined by the elemental forms of perceptual processing the SC has supported since before there was a neocortex.

neuroscience↗

A causal role for mouse superior colliculus in visual perceptual decision-making

The superior colliculus (SC) is arguably the most important visual structure in the mouse brain and is well-known for its involvement in innate responses to visual threats and prey items. In other species, the SC plays a central role in voluntary as well as innate visual functions, including crucial contributions to selective attention and perceptual decision-making. In the mouse, the possible role of the SC in voluntary visual choice behaviors has not been established. Here, we demonstrate that the mouse SC plays a causal role in visual perceptual decision-making by transiently inhibiting SC activity during an orientation-change detection task. First, unilateral SC inhibition induced spatially specific deficits in detection. Hit rates were reduced and reaction times increased for orientation changes in the contralateral but not ipsilateral visual field. Second, the deficits caused by SC inhibition were specific to a temporal epoch coincident with early visual burst responses in the SC. Inhibiting SC during this 100-ms period caused a contralateral detection deficit, whereas inhibition immediately before or after did not. Third, SC inhibition reduced visual detection sensitivity. Psychometric analysis revealed that inhibiting SC visual activity significantly increased detection thresholds for contralateral orientation changes. In addition, effects on detection thresholds and lapse rates caused by SC inhibition were larger in the presence of a competing visual stimulus, indicating a role for the mouse SC in visual target selection. Together, our results demonstrate that the mouse SC plays a crucial role in voluntary visual choice behaviors. Significance statementThe mouse superior colliculus has become a popular model for studying the circuit organization and development of the visual system. Although the SC is a fundamental component of the visual pathways in mice, its role in visual perceptual decision-making is not clear. By investigating how temporally precise SC inhibition influenced behavioral performance during a visually guided orientation change detection task, we identified a 100-ms temporal epoch of SC visual activity that is crucial for the ability of mice to detect behaviorally relevant visual changes. In addition, we found that SC inhibition also caused deficits in visual target selection. Thus, our findings highlight the importance of the SC for visual perceptual choice behavior in the mouse.

animal behavior and cognition↗

Focal disruption of temporal cortex in macaque during midbrain-induced neglect

Spatial neglect is a common clinical syndrome involving disruption of the brains attention-related circuitry, including the dorsocaudal temporal cortex. While neglect is readily modeled in macaques, the absence of evidence for temporal cortex involvement has suggested a fundamental difference from humans. To map the neurological expression of spatial neglect in macaques, we measured attention-related fMRI activity across the cerebral cortex during experimental induction of neglect through reversible inactivation of the superior colliculus. During inactivation, monkeys exhibited hallmark attentional deficits of neglect in tasks using either moving or static stimuli. The behavioral deficits were accompanied by marked reductions in fMRI attentional modulation that were strongest in a small region on the floor of the superior temporal sulcus. Notably, direct inactivation of this mid-STS cortical region caused similar neglect-like spatial attention deficits. These results identify a putative macaque homolog to temporal cortex structures known to play a central role in human neglect.\n\nHighlightsO_LIDuring neglect the mid-STS cortex shows largest reduction in attentional modulation\nC_LIO_LIThe mid-STS cortex is selectively affected with static as well as dynamic stimuli\nC_LIO_LIMid-STS cortex is affected during neglect caused by SC or FEF inactivation\nC_LIO_LIInactivation of mid-STS cortex itself causes neglect without eye movement deficits\nC_LI\n\nIn BriefUsing fMRI in macaques performing attention tasks combined with reversible inactivations, Bogadhi et al. provide causal evidence that a region on the floor of the superior temporal sulcus is a crucial node in the cortical control of covert selective attention and a putative homolog to temporal cortex regions in humans implicated in spatial neglect.

neuroscience↗

Brain regions modulated during covert visual attention in the macaque

Neurophysiology studies of covert visual attention in monkeys have emphasized the modulation of sensory neural responses in the visual cortex. At the same time, electrophysiological correlates of attention have been reported in other cortical and subcortical structures, and recent fMRI studies have identified regions across the brain modulated by attention. Here we used fMRI in two monkeys performing covert attention tasks to reproduce and extend these findings in order to help establish a more complete list of brain structures involved in the control of attention. As expected from previous studies, we found attention-related modulation in frontal, parietal and visual cortical areas as well as the superior colliculus and pulvinar. We also found significant attention-related modulation in cortical regions not traditionally linked to attention - mid-STS areas (anterior FST and parts of IPa, PGa, TPO), as well as the caudate nucleus. A control experiment using a second-order orientation stimulus showed that the observed modulation in a subset of these mid-STS areas did not depend on visual motion. These results identify the mid-STS areas (anterior FST and parts of IPa, PGa, TPO) and caudate nucleus as potentially important brain regions in the control of covert visual attention in monkeys.

animal behavior and cognition↗