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Teh, K. L.

Publications and source records attributed to Teh, K. L..

7 recordsLinked to original sources

Coordinated orienting behavior emerges following unilateral optogenetic activation of Superior Colliculus GABAergic neurons

Orienting coordinates movements of the eyes, whiskers, nose, and other effectors, but how the superior colliculus (SC) recruits these components over time remains unclear. We combined unilateral optogenetic activation of SC GABAergic neurons with high-speed tracking of facial movements and Neuropixels recordings to examine SC-evoked orienting in head-fixed mice. Stimulation recruited movements of the whiskers, nose, eyes, and pupil. Horizontal eye and nose movements were directed contralateral to the stimulated hemisphere, whereas vertical eye movements, pupil dilation, and whisker protraction did not differ significantly between stimulation sides. Nose and whisker movements generally preceded eye movements, followed by slower pupil dilation, revealing a temporally organized response. Recordings from the SC contralateral to the stimulated hemisphere revealed heterogeneous neuronal responses comprising short-latency excitation and delayed excitation or inhibition. Short-latency excitation was similar on trials with and without evoked movements, whereas delayed excitation was greater on trials that evoked eye or nose movements. Neurons modulated during spontaneous nose movements showed corresponding optogenetically evoked responses, linking stimulation-induced activity to endogenous movement-related activity. Thus, activation of SC GABAergic neurons initiates evolving population activity that recruits a coordinated sequence of orienting movements.

neuroscience↗

Thalamocortical, not Intracortical, Inputs Set the Wakeful Activity Levels of Cortical Visual Inhibition

Cortical neurons integrate from a wide range of synaptic inputs, locally within the cortex and distally from multiple brain sources, which altogether support the generation and transmission of spikes. Yet, the relative influence on local cortical processing between thalamocortical and intracortical inputs still remains poorly understood. Here, we used tangential insertion of high-density silicon probes to capture thalamocortical next to intracortical functional connectivity, thereby unraveling their relative contribution to local cortical dynamics. By comparing wakefulness versus light anesthesia, we revealed a marked wakeful increase of firing in specifically thalamocortical axons and putative cortical inhibitory neurons; an increase which is very homogeneous in both populations, and comparatively absent in neighboring cortical excitatory neurons. Such specific comodulation is attributable to the known preferential connectivity of thalamocortical axons toward putative cortical inhibitory neurons, which we quantified to follow a 90/10% preference. In addition, we uncovered that wakeful increases of activity levels are symmetric in thalamocortical synapses and asymmetric in intracortical synapses. Indeed, within intracortical synapses, the wakeful increases of firing mostly happen in receiving neurons, leaving pre-synaptic upstream neurons barely impacted by wakefulness. In the meantime, thalamocortical receiving excitatory neurons exhibit a marked wakeful increase of firing, unlike the rest of the excitatory cortical population. Using mathematical modelling simulating spike transmission in thalamocortical and intracortical networks, we showed that only outnumbering thalamocortical-to-intracortical inputs could mimic the observed homogeneous wakeful increases of firing in thalamocortical and cortical inhibitory neurons. Altogether, our results identify thalamocortical synaptic inputs as a key controller of the wakeful level of firing of inhibitory neurons at the first relay of visual cortical processing.

neuroscience↗

Synergistic effects of presynaptic and postsynaptic neurons give rise to three-stage short-term plasticity in vivo

Short-term plasticity (STP) is the transient fluctuation of connection strength between two neurons depending on the recent history of neuronal activity. STP shapes neurotransmission over time and plays important roles in circuit computations. It is classically quantified ex vivo either at the synaptic level or at the level of spike transmission from the presynaptic neuron to the postsynaptic neuron. However, the exact relationship between the postsynaptic dendritic responses and spike transmission during STP still remains unclear in vivo. Here, we characterized together the STP of both postsynaptic dendritic responses, measured by the postsynaptic field potential (PFP), and spike transmission at the retinocollicular pathway of mice. We found mostly facilitating STP, where the second presynaptic spike occurring within 25 ms induces a larger PFP, and consequently a higher postsynaptic firing rate compared to responses from the first presynaptic spike. Both PFP and spike transmission exhibit short-term facilitation, but to a different degree, where the facilitation in the spike transmission is larger than the PFP. The PFP and spike transmission also exhibit facilitation of different decay time constants, indicating a nonlinear relationship between the two. Interestingly, a preceding postsynaptic spike can induce a similarly large but longer lasting facilitation on the spike transmission upon receiving a subsequent presynaptic input. However, STP of the PFP does not depend on the preceding postsynaptic spike, suggesting that this longer postsynaptic facilitation has a nonsynaptic origin. Overall, our results indicate that STP of the retinocollicular pathway exhibits three different stages: 1) a weak synaptic facilitation of postsynaptic dendritic responses, 2) a strong synaptic facilitation of spike transmission, and 3) a longer lasting nonsynaptic facilitation of spike transmission. Using a computational model, we show that the second STP stage is a direct inheritance from the first STP stage, whereas two opposing nonsynaptic mechanisms with different time constants are needed for the emergence of the third STP stage. These findings provide direct evidence that synaptic and nonsynaptic STPs coexist in vivo, paving the way for large-scale measurement of these STPs and offering a means to monitor the transmission of information in neural circuits of behaving animals.

neuroscience↗

Differential Short-Term Facilitation Of Synaptic Inputs And Spike Transmission At The Retinocollicular Synapse In Vivo

Short-term plasticity (STP) is important for understanding how neuronal circuits can perform different computations. The STP of a neuron pair can be measured directly using paired whole-cell recordings. Besides, the cross-correlation between the presynaptic and postsynaptic neuronal firing is usually used as a proxy for estimating the synaptic properties. However, the relationships between the synaptic inputs and the spiking properties of the postsynaptic neurons during the STP in vivo still remain unclear. Here, we characterized the STP of both synaptic input, measured by the postsynaptic field potential (PFP), and spike transmission at the retinocollicular pathway of mice. We found that the STP of the retinocollicular pathway is mainly facilitating, where the second presynaptic spike induces a larger PFP and higher postsynaptic firing rate than the first presynaptic spike. The facilitation in the postsynaptic firing rate is generally larger than the PFP facilitation. Interestingly, the last postsynaptic spike timing also has a large facilitating effect on the postsynaptic spiking upon receiving a presynaptic input spike. However, the PFP does not depend on the last postsynaptic spike timing, suggesting that there is an input-independent component of spike transmission in STP. Overall, our results indicate that the STP of the retinocollicular pathway is likely a two-stage process, where the spiking plasticity of the postsynaptic neuron could be independent of its inputs. HighlightsO_LIMeasure the short-term plasticity of the postsynaptic dendritic response and the spike transmission simultaneously C_LIO_LIThe retinocollicular pathway exhibits paired-spike facilitation C_LIO_LISpike transmission facilitates more than postsynaptic dendritic response C_LIO_LIShort last postsynaptic spike time facilitates spike transmission independent of the next presynaptic input C_LI

neuroscience↗

Retinal waves align the concentric orientation map in mouse superior colliculus to the center of vision

Neurons in the mouse superior colliculus (SC) are arranged in an orientation preference map that has a concentric organization, which is aligned to the center of vision and the optic flow experienced by the mouse. The developmental mechanisms that underlie this functional map remain unclear. Here, we propose that the spatiotemporal properties of spontaneous retinal waves during development provide a scaffold to establish the concentric orientation map in the mouse SC and its alignment to the optic flow. We test this hypothesis by modelling the orientation-tuned SC neurons that receive ON/OFF retinal inputs. Our results suggest that the stage III retinal wave properties, namely OFF delayed response and the wave propagation direction bias, are key factors that regulate the spatial organization of the SC orientation map. Specifically, the OFF delay mediates the establishment of orientation-tuned SC neurons by segregating their ON/OFF receptive subfields, the wave-like activities facilitate the formation of a concentric pattern, and the wave direction biases align the orientation map to the center of vision. Taken together, our model suggests that retinal waves may play an instructive role in establishing functional properties of SC neurons and provides a promising mechanism for explaining the correlations between the optic flow and the SC orientation map.

neuroscience↗

Strong and specific connections between retinal axon mosaics and midbrain neurons revealed by large scale paired recordings

The superior colliculus (SC) is a midbrain structure that plays important roles in visually guided behaviors. Neurons in the SC receive afferent inputs from retinal ganglion cells (RGC), the output cells of the retina, but how SC neurons integrate RGC activity in vivo is unknown. SC neurons might be driven by strong but sparse retinal inputs, thereby reliably transmitting specific retinal functional channels. Alternatively, SC neurons could sum numerous but weak inputs, thereby extracting new features by combining a diversity of retinal signals. Here, we discovered that high-density electrodes simultaneously capture the activity and the location of large populations of retinal axons and their postsynaptic SC target neurons, permitting us to investigate the retinocollicular circuit on a structural and functional level in vivo. We show that RGC axons in the mouse are organized in mosaics that provide a single cell precise representation of the retina as input to SC. This isomorphic mapping between retina and SC builds the scaffold for highly specific wiring in the retinocollicular circuit which we show is characterized by strong connections and limited functional convergence, established in log-normally distributed connection strength. Because our novel method of large-scale paired recordings is broadly applicable for investigating functional connectivity across brain regions, we were also able to identify retinal inputs to the avian optic tectum of the zebra finch. We found common wiring rules in mammals and birds that provide a precise and reliable representation of the visual world encoded in RGCs to neurons in retinorecipient areas. HIGHLIGHTSO_LIHigh-density electrodes capture the activity of afferent axons and target neurons in vivo C_LIO_LIRetinal ganglion cells axons are organized in mosaics C_LIO_LISingle cell precise isomorphism between dendritic and axonal RGC mosaics C_LIO_LIMidbrain neurons are driven by sparse but strong retinal inputs C_LIO_LIFunctional wiring of the retinotectal circuit is similar in mammals and birds C_LI

neuroscience↗

Tangential high-density electrode insertions allow to simultaneously measure neuronal activity across an extended region of the visual field in mouse superior colliculus

The superior colliculus (SC) is a midbrain structure that plays a central role in visual processing. Although we have learned a considerable amount about the function of single SC neurons, the way in which sensory information is represented and processed on the population level in awake behaving animals and across a large region of the retinotopic map is still largely unknown. Partially because the SC is anatomically located below the cortical sheet and the transverse sinus, it is technically difficult to measure neuronal activity from a large population of neurons in SC. To address this, we propose a tangential recording configuration using high-density electrode probes (Neuropixels) in mouse SC in vivo that permits a large number of recording sites (~200) accessibility inside the SC circuitry. This approach thereby provides a unique opportunity to measure the activity of SC neuronal populations composing up to ~2 mm of SC tissue and characterized by receptive fields covering an extended region in the visual field. Here we describe how to perform tangential recordings along the anterior-posterior and the medio-lateral axis of the mouse SC in vivo and how to combine this approach with optogenetic tools for cell-type identification on the population level.

neuroscience↗