Visual recognition of social signals by a tectothalamic neural circuit.

Social affiliation emerges from individual-level behavioural rules that are driven by conspecific signals1-5. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred interanimal distance in swarms6-8. However, little is known about their perceptual mechanisms and executive neural circuits3. Here we trace the neuronal response to self-like biological motion9,10, a visual trigger for affiliation in developing zebrafish2,11. Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 21 activity hotspots distributed throughout the brain as well as clustered biological-motion-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus. Individual dorsal thalamus neurons encode local acceleration of visual stimuli mimicking typical fish kinetics but are insensitive to global or continuous motion. Electron microscopic reconstruction of dorsal thalamus neurons revealed synaptic input from the optic tectum and projections into hypothalamic areas with conserved social function12-14. Ablation of the optic tectum or dorsal thalamus selectively disrupted social attraction without affecting short-distance repulsion. This tectothalamic pathway thus serves visual recognition of conspecifics, and dissociates neuronal control of attraction from repulsion during social affiliation, revealing a circuit underpinning collective behaviour.

Laminar distribution and arbor density of two functional classes of thalamic inputs to primary visual cortex.

Motion/direction-sensitive and location-sensitive neurons are the two major functional types in mouse visual thalamus that project to the primary visual cortex (V1). It is under debate whether motion/direction-sensitive inputs preferentially target the superficial layers in V1, as opposed to the location-sensitive inputs, which preferentially target the middle layers. Here, by using calcium imaging to measure the activity of motion/direction-sensitive and location-sensitive axons in V1, we find evidence against these cell-type-specific laminar biases at the population level. Furthermore, using an approach to reconstruct axon arbors with identified in vivo response types, we show that, at the single-axon level, the motion/direction-sensitive axons project more densely to the middle layers than the location-sensitive axons. Overall, our results demonstrate that motion/direction-sensitive thalamic neurons project extensively to the middle layers of V1 at both the population and single-cell levels, providing further insight into the organization of thalamocortical projection in the mouse visual system.

Differential cortical and subcortical projection targets of subfields in the core region of mouse auditory cortex.

The core region of the rodent auditory cortex has two areas: the primary auditory area (A1) and the anterior auditory field (AAF). However, the functional difference between these areas is unclear. To elucidate this issue, here we studied the projections from A1 and AAF in mice using adeno-associated virus (AAV) vectors expressing either a green fluorescent protein or a red fluorescent protein. After mapping A1 and AAF using optical imaging, we injected a distinct AAV vector into each of the two fields at a frequency-matched high-frequency location. We found that A1 and AAF projected commonly to virtually all target areas examined, but each field had its own preference for projection targets. Frontal and parietal regions were the major cortical targets: in the frontal cortex, A1 and AAF showed dominant projections to the anterior cingulate cortex Cg1 and the secondary motor cortex (M2), respectively; in the parietal cortex, A1 and AAF exhibited dense projections to the medial secondary visual cortex and the posterior parietal cortex (PPC), respectively. Although M2 and PPC received considerable input from A1 as well, A1 innervated the medial part whereas AAF innervated the lateral part of these cortical regions. A1 also projected to the orbitofrontal cortex, while AAF also projected to the primary somatosensory cortex and insular auditory cortex. As for subcortical projections, A1 and AAF projected to a common ventromedial region in the caudal striatum with a comparable strength; they also both projected to the medial geniculate body and the inferior colliculus, innervating common and distinct divisions of the nuclei. A1 also projected to visual subcortical structures, such as the superior colliculus and the lateral posterior nucleus of the thalamus, where fibres from AAF were sparse. Our results demonstrate the preference of A1 and AAF for cortical and subcortical targets, and for divisions in individual target. The preference of A1 and AAF for sensory-related structures suggest a role for A1 in providing auditory information for audio-visual association at both the cortical and subcortical level, and a distinct role of AAF in providing auditory information for association with somatomotor information in the cortex.

Energy-efficient information transfer at thalamocortical synapses.

We have previously shown that the physiological size of postsynaptic currents maximises energy efficiency rather than information transfer across the retinothalamic relay synapse. Here, we investigate information transmission and postsynaptic energy use at the next synapse along the visual pathway: from relay neurons in the thalamus to spiny stellate cells in layer 4 of the primary visual cortex (L4SS). Using both multicompartment Hodgkin-Huxley-type simulations and electrophysiological recordings in rodent brain slices, we find that increasing or decreasing the postsynaptic conductance of the set of thalamocortical inputs to one L4SS cell decreases the energy efficiency of information transmission from a single thalamocortical input. This result is obtained in the presence of random background input to the L4SS cell from excitatory and inhibitory corticocortical connections, which were simulated (both excitatory and inhibitory) or injected experimentally using dynamic-clamp (excitatory only). Thus, energy efficiency is not a unique property of strong relay synapses: even at the relatively weak thalamocortical synapse, each of which contributes minimally to the output firing of the L4SS cell, evolutionarily-selected postsynaptic properties appear to maximise the information transmitted per energy used.

Cell-type-Specific Patterned Stimulus-Independent Neuronal Activity in the Drosophila Visual System during Synapse Formation.

Stereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in the Drosophila visual system during synaptogenesis. Using in vivo calcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 of over 100 specific neuron types in the fly visual system examined exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell-type-specific activity coordinates the development of the functional circuitry of the adult brain.

Lateral geniculate neurons projecting to primary visual cortex show ocular dominance plasticity in adult mice.

Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca2+ imaging of thalamic afferents in layer 1 of binocular visual cortex, we provide evidence against this tenet: the respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced ocular dominance (OD) shifts after monocular deprivation in adult mice. Most (86%), but not all, of dLGN cell boutons were monocular during normal visual experience. Following deprivation, initially deprived-eye-dominated boutons reduced or lost their visual responsiveness to that eye and frequently became responsive to the non-deprived eye. This cannot be explained by eye-specific cortical changes propagating to dLGN via cortico-thalamic feedback because the shift in dLGN responses was largely resistant to cortical inactivation using the GABAA receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partially reflect plasticity of eye-specific inputs onto dLGN neurons.

Binocular matching of thalamocortical and intracortical circuits in the mouse visual cortex.

Visual cortical neurons are tuned to similar orientations through the two eyes. The binocularly-matched orientation preference is established during a critical period in early life, but the underlying circuit mechanisms remain unknown. Here, we optogenetically isolated the thalamocortical and intracortical excitatory inputs to individual layer 4 neurons and studied their binocular matching. In adult mice, the thalamic and cortical inputs representing the same eyes are similarly tuned and both are matched binocularly. In mice before the critical period, the thalamic input is already slightly matched, but the weak matching is not manifested due to random connections in the cortex, especially those serving the ipsilateral eye. Binocular matching is thus mediated by orientation-specific changes in intracortical connections and further improvement of thalamic matching. Together, our results suggest that the feed-forward thalamic input may play a key role in initiating and guiding the functional refinement of cortical circuits in critical period development.

Microconnectomics of the pretectum and ventral thalamus in the chicken (Gallus gallus).

The avian pretectal and ventrothalamic nuclei, encompassing the griseum tectale (GT), n. lentiformis mesencephali (LM), and n. geniculatus lateralis pars ventralis (GLv), are prominent retinorecipient structures related to optic flow operations and visuomotor control. Hence, a close coordination of these neural circuits is to be expected. Yet the connectivity among these nuclei is poorly known. Here, using intracellular labeling and in situ hybridization, we investigated the detailed morphology, connectivity, and neurochemical identity of neurons in these nuclei. Two different cell types exist in the GT: one that generates an axonal projection to the optic tectum (TeO), LM, GLv, and n. intercalatus thalami (ICT), and a second population that only projects to the LM and GLv. In situ hybridization revealed that most neurons in the GT express the vesicular glutamate transporter (VGluT2) mRNA, indicating a glutamatergic identity. In the LM, three morphological cell types were defined, two of which project axons towards dorsal targets. The LM neurons showed strong VGluT2 expression. Finally, the cells located in the GLv project to the TeO, LM, GT, n. principalis precommisuralis (PPC), and ICT. All neurons in the GLv showed strong expression of the vesicular inhibitory amino acid transporter (VIAAT) mRNA, suggesting a GABAergic identity. Our results show that the pretectal and ventrothalamic nuclei are highly interconnected, especially by glutamatergic and GABAergic neurons from the GT and GLv, respectively. This complex morphology and connectivity might be required to organize orienting visuomotor behaviors and coordinate the specific optic flow patterns that they induce. J. Comp. Neurol. 524:2208-2229, 2016. © 2015 Wiley Periodicals, Inc.

Laminar differences in the orientation selectivity of geniculate afferents in mouse primary visual cortex.

It has been debated whether orientation selectivity in mouse primary visual cortex (V1) is derived from tuned lateral geniculate nucleus (LGN) inputs or computed from untuned LGN inputs. However, few studies have measured orientation tuning of LGN axons projecting to V1. We measured the response properties of mouse LGN axons terminating in V1 and found that LGN axons projecting to layer 4 were generally less tuned for orientation than axons projecting to more superficial layers of V1. We also found several differences in response properties between LGN axons and V1 neurons in layer 4. These results suggest that orientation selectivity of mouse V1 may not simply be inherited from LGN inputs, but could also depend on thalamocortical or V1 circuits.

Asymmetric top-down modulation of ascending visual pathways in pigeons.

Cerebral asymmetries are a ubiquitous phenomenon evident in many species, incl. humans, and they display some similarities in their organization across vertebrates. In many species the left hemisphere is associated with the ability to categorize objects based on abstract or experience-based behaviors. Using the asymmetrically organized visual system of pigeons as an animal model, we show that descending forebrain pathways asymmetrically modulate visually evoked responses of single thalamic units. Activity patterns of neurons within the nucleus rotundus, the largest thalamic visual relay structure in birds, were differently modulated by left and right hemispheric descending systems. Thus, visual information ascending towards the left hemisphere was modulated by forebrain top-down systems at thalamic level, while right thalamic units were strikingly less modulated. This asymmetry of top-down control could promote experience-based processes within the left hemisphere, while biasing the right side towards stimulus-bound response patterns. In a subsequent behavioral task we tested the possible functional impact of this asymmetry. Under monocular conditions, pigeons learned to discriminate color pairs, so that each hemisphere was trained on one specific discrimination. Afterwards the animals were presented with stimuli that put the hemispheres in conflict. Response patterns on the conflicting stimuli revealed a clear dominance of the left hemisphere. Transient inactivation of left hemispheric top-down control reduced this dominance while inactivation of right hemispheric top-down control had no effect on response patterns. Functional asymmetries of descending systems that modify visual ascending pathways seem to play an important role in the superiority of the left hemisphere in experience-based visual tasks.

Thalamic projections to visual and visuomotor areas (V6 and V6A) in the Rostral Bank of the parieto-occipital sulcus of the Macaque.

The medial posterior parietal cortex of the primate brain includes different functional areas, which have been defined based on the functional properties, cyto- and myeloarchitectural criteria, and cortico-cortical connections. Here, we describe the thalamic projections to two of these areas (V6 and V6A), based on 14 retrograde neuronal tracer injections in 11 hemispheres of 9 Macaca fascicularis. The injections were placed either by direct visualisation or using electrophysiological guidance, and the location of injection sites was determined post mortem based on cyto- and myeloarchitectural criteria. We found that the majority of the thalamic afferents to the visual area V6 originate in subdivisions of the lateral and inferior pulvinar nuclei, with weaker inputs originating from the central densocellular, paracentral, lateral posterior, lateral geniculate, ventral anterior and mediodorsal nuclei. In contrast, injections in both the dorsal and ventral parts of the visuomotor area V6A revealed strong inputs from the lateral posterior and medial pulvinar nuclei, as well as smaller inputs from the ventrolateral complex and from the central densocellular, paracentral, and mediodorsal nuclei. These projection patterns are in line with the functional properties of injected areas: "dorsal stream" extrastriate area V6 receives information from visuotopically organised subdivisions of the thalamus; whereas visuomotor area V6A, which is involved in the sensory guidance of arm movement, receives its primary afferents from thalamic nuclei that provide high-order somatic and visual input.

Multiple Retinal Axons Converge onto Relay Cells in the Adult Mouse Thalamus.

Activity-dependent refinement of neural circuits is a fundamental principle of neural development. This process has been well studied at retinogeniculate synapses-synapses that form between retinal ganglion cells (RGCs) and relay cells within the dorsal lateral geniculate nucleus. Physiological studies suggest that shortly after birth, inputs from ∼20 RGCs converge onto relay cells. Subsequently, all but just one to two of these inputs are eliminated. Despite widespread acceptance, this notion is at odds with ultrastructural studies showing numerous retinal terminals clustering onto relay cell dendrites in the adult. Here, we explored this discrepancy using brainbow AAVs and serial block face scanning electron microscopy (SBFSEM). Results with both approaches demonstrate that terminals from numerous RGCs cluster onto relay cell dendrites, challenging the notion that only one to two RGCs innervate each relay cell. These findings force us to re-evaluate our understanding of subcortical visual circuitry.

Organization and number of orexinergic neurons in the hypothalamus of two species of Cetartiodactyla: a comparison of giraffe (Giraffa camelopardalis) and harbour porpoise (Phocoena phocoena).

The present study describes the organization of the orexinergic (hypocretinergic) neurons in the hypothalamus of the giraffe and harbour porpoise--two members of the mammalian Order Cetartiodactyla which is comprised of the even-toed ungulates and the cetaceans as they share a monophyletic ancestry. Diencephalons from two sub-adult male giraffes and two adult male harbour porpoises were coronally sectioned and immunohistochemically stained for orexin-A. The staining revealed that the orexinergic neurons could be readily divided into two distinct neuronal types based on somal volume, area and length, these being the parvocellular and magnocellular orexin-A immunopositive (OxA+) groups. The magnocellular group could be further subdivided, on topological grounds, into three distinct clusters--a main cluster in the perifornical and lateral hypothalamus, a cluster associated with the zona incerta and a cluster associated with the optic tract. The parvocellular neurons were found in the medial hypothalamus, but could not be subdivided, rather they form a topologically amorphous cluster. The parvocellular cluster appears to be unique to the Cetartiodactyla as these neurons have not been described in other mammals to date, while the magnocellular nuclei appear to be homologous to similar nuclei described in other mammals. The overall size of both the parvocellular and magnocellular neurons (based on somal volume, area and length) were larger in the giraffe than the harbour porpoise, but the harbour porpoise had a higher number of both parvocellular and magnocellular orexinergic neurons than the giraffe despite both having a similar brain mass. The higher number of both parvocellular and magnocellular orexinergic neurons in the harbour porpoise may relate to the unusual sleep mechanisms in the cetaceans.

Different glutamate receptors convey feedforward and recurrent processing in macaque V1.

Neurons in the primary visual cortex (V1) receive feedforward input from the thalamus, which shapes receptive-field properties. They additionally receive recurrent inputs via horizontal connections within V1 and feedback from higher visual areas that are thought to be important for conscious visual perception. Here, we investigated what roles different glutamate receptors play in conveying feedforward and recurrent inputs in macaque V1. As a measure of recurrent processing, we used figure-ground modulation (FGM), the increased activity of neurons representing figures compared with background, which depends on feedback from higher areas. We found that feedforward-driven activity was strongly reduced by the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas this drug had no effect on FGM. In contrast, blockers of the NMDA receptor reduced FGM, whereas their effect on visually driven activity varied with the subunit specificity of the drug. The NMDA receptor blocker 2-amino-5-phosphonovalerate (APV) caused a slight reduction of the visual response, whereas ifenprodil, which targets NMDA receptors containing the NMDA receptor NR2B subunit, increased the visual response. These findings demonstrate that glutamate receptors contribute differently to feedforward and recurrent processing in V1 and suggest ways to selectively disrupt recurrent processing so that its role in visual perception can be elucidated.

Defining the computational structure of the motion detector in Drosophila.

Many animals rely on visual motion detection for survival. Motion information is extracted from spatiotemporal intensity patterns on the retina, a paradigmatic neural computation. A phenomenological model, the Hassenstein-Reichardt correlator (HRC), relates visual inputs to neural activity and behavioral responses to motion, but the circuits that implement this computation remain unknown. By using cell-type specific genetic silencing, minimal motion stimuli, and in vivo calcium imaging, we examine two critical HRC inputs. These two pathways respond preferentially to light and dark moving edges. We demonstrate that these pathways perform overlapping but complementary subsets of the computations underlying the HRC. A numerical model implementing differential weighting of these operations displays the observed edge preferences. Intriguingly, these pathways are distinguished by their sensitivities to a stimulus correlation that corresponds to an illusory percept, "reverse phi," that affects many species. Thus, this computational architecture may be widely used to achieve edge selectivity in motion detection.

The retinohypothalamic tract: comparison of axonal projection patterns from four major targets.

The retinohypothalamic tract is one component of the optic nerve that transmits information about environmental luminance levels through medial and lateral branches to four major terminal fields in the hypothalamus. The spatial distribution and organization of axonal projections from each of these four terminal fields were analyzed and compared systematically with the anterograde pathway tracer PHAL in rats where the terminal fields had been labeled with intravitreal injections of a different anterograde pathway tracer, CTb. First, the well-known projections of two medial retinohypothalamic tract targets (the ventrolateral suprachiasmatic nucleus and perisuprachiasmatic region) were confirmed and extended. They share qualitatively similar projections to a well-known set of brain regions thought to control circadian rhythms. Second, the projections of a third medial tract target, the ventromedial part of the anterior hypothalamic nucleus, were analyzed for the first time and shown to resemble qualitatively those from the suprachiasmatic nucleus and perisuprachiasmatic region. And third, projections from the major lateral retinohypothalamic tract target were analyzed for the first time and shown to be quite different from those associated with medial tract targets. This target is a distinct core part of the ventral zone of the anterior group of the lateral hypothalamic area that lies just dorsal to the caudal two-thirds of the supraoptic nucleus. Its axonal projections are to neural networks that control a range of specific goal-oriented behaviors (especially drinking, reproductive, and defensive) along with adaptively appropriate and complementary visceral responses and adjustments to behavioral state.

Hyperbaric oxygen preconditioning promotes survival of retinal ganglion cells in a rat model of optic nerve crush.

In this study we tested the hypothesis that hyperbaric oxygen preconditioning (HBO-PC) reduces retinal neuronal death due to optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC accompanied by a contralateral sham operation. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atmospheres absolute (ATA) for 1 h every 12 h for 2 days prior to ONC. The rats were euthanized at 1 or 2 weeks after ONC. Retinal ganglion cell (RGC) density was counted by hematoxylin and eosin (H&E) staining of the retina and retrograde labeling with FluoroGold application to the superior colliculus. Visual function was assessed by flash visual evoked potentials (FVEP). TUNEL straining and caspase-3 and caspase-9 activity in the retinas were assessed. The RGC density in the retinas of ONC HBO-PC-treated rats was significantly higher than that of the corresponding ONC-only rats (the survival rate was 67.2% versus 49.7% by H&E staining, and 60.3% versus 28.9% by retrograde labeling with FluoroGold, respectively; p < 0.01) at 2 weeks after ONC. FVEP measurements indicated a significantly better preserved latency and amplitude of the P1 wave in the ONC HBO-PC-treated rats than the ONC-only rats (92 +/- 7 msec, 21 +/- 3 microv in the sham-operated group, 117 +/- 12 msec, 14 +/- 2 microv in the HBO-PC-treated group, and 169 +/- 15 msec, 7 +/- 1 microv in the corresponding ONC group; p < 0.01). TUNEL assays showed fewer apoptotic cells in the HBO-PC-treated group, accompanied by the suppression of caspase-3 and caspase-9 activity. These results demonstrate that HBO-PC appears to be neuroprotective against ONC insult via inhibition of neuronal apoptosis pathways.

Loss of potassium homeostasis underlies hyperthermic conduction failure in control and preconditioned locusts.

At extreme temperature, neurons cease to function appropriately. Prior exposure to a heat stress (heat shock [HS]) can extend the temperature range for action potential conduction in the axon, but how this occurs is not well understood. Here we use electrophysiological recordings from the axon of a locust visual interneuron, the descending contralateral movement detector (DCMD), to examine what physiological changes result in conduction failure and what modifications allow for the observed plasticity following HS. We show that at high temperature, conduction failure in the DCMD occurred preferentially where the axon passes through the thoracic ganglia rather than in the connective. Although the membrane potential hyperpolarized with increasing temperature, we observed a modest depolarization (3-6 mV) in the period preceding the failure. Prior to the conduction block, action potential amplitude decreased and half-width increased. Both of these failure-associated effects were attenuated following HS. Extracellular potassium concentration ([K+]o) increased sharply at failure and the failure event could be mimicked by the application of high [K+]o. Surges in [K+]o were muted following HS, suggesting that HS may act to stabilize ion distribution. Indeed, experimentally increased [K+]o lowered failure temperature significantly more in control animals than in HS animals and experimentally maintained [K+]o was found to be protective. We suggest that the more attenuated effects of failure on the membrane properties of the DCMD axon in HS animals is consistent with a decrease in the disruptive nature of the [K+]o-dependent failure event following HS and thus represents an adaptive mechanism to cope with thermal stress.

Lagged cells in alert monkey lateral geniculate nucleus.

Five lagged cells were recognized by extracellular recording in the lateral geniculate nucleus of an awake, behaving macaque monkey. Previous reports of lagged cells were all in the anesthetized cat. Both parvocellular and magnocellular lagged cells were observed. Response timing was distributed continuously across the population, and both sustained and transient responses were seen in the magnocellular subpopulation. Cortex thus receives signals with a wide range of timing, which can mediate direction selectivity across multiple dimensions.