Corticotectal Projections Research Articles

Manipulating the Level of Sensorimotor Stimulation during LI-rTMS Can Improve Visual Circuit Reorganisation in Adult Ephrin-A2A5-/- Mice.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has the potential to treat a variety of neurologic and psychiatric disorders. The extent of rTMS-induced neuroplasticity may be dependent on a subject’s brain state at the time of stimulation. Chronic low intensity rTMS (LI-rTMS) has previously been shown to induce beneficial structural and functional reorganisation within the abnormal visual circuits of ephrin-A2A5-/- mice in ambient lighting. Here, we administered chronic LI-rTMS in adult ephrin-A2A5-/- mice either in a dark environment or concurrently with voluntary locomotion. One day after the last stimulation session, optokinetic responses were assessed and fluorescent tracers were injected to map corticotectal and geniculocortical projections. We found that LI-rTMS in either treatment condition refined the geniculocortical map. Corticotectal projections were improved in locomotion+LI-rTMS subjects, but not in dark + LI-rTMS and sham groups. Visuomotor behaviour was not improved in any condition. Our results suggest that the beneficial reorganisation of abnormal visual circuits by rTMS can be significantly influenced by simultaneous, ambient visual input and is enhanced by concomitant physical exercise. Furthermore, the observed pathway-specific effects suggest that regional molecular changes and/or the relative proximity of terminals to the induced electric fields influence the outcomes of LI-rTMS on abnormal circuitry.

Organization of the inputs and outputs of the mouse superior colliculus

The superior colliculus (SC) receives diverse and robust cortical inputs to drive a range of cognitive and sensorimotor behaviors. However, it remains unclear how descending cortical input arising from higher-order associative areas coordinate with SC sensorimotor networks to influence its outputs. Here, we construct a comprehensive map of all cortico-tectal projections and identify four collicular zones with differential cortical inputs: medial (SC.m), centromedial (SC.cm), centrolateral (SC.cl) and lateral (SC.l). Further, we delineate the distinctive brain-wide input/output organization of each collicular zone, assemble multiple parallel cortico-tecto-thalamic subnetworks, and identify the somatotopic map in the SC that displays distinguishable spatial properties from the somatotopic maps in the neocortex and basal ganglia. Finally, we characterize interactions between those cortico-tecto-thalamic and cortico-basal ganglia-thalamic subnetworks. This study provides a structural basis for understanding how SC is involved in integrating different sensory modalities, translating sensory information to motor command, and coordinating different actions in goal-directed behaviors.

Corticotectal Projections From the Premotor or Primary Motor Cortex After Cortical Lesion or Parkinsonian Symptoms in Adult Macaque Monkeys: A Pilot Tracing Study.

The corticotectal projections, together with the corticobulbar (corticoreticular) projections, work in parallel with the corticospinal tract (CST) to influence motoneurons in the spinal cord both directly and indirectly via the brainstem descending pathways. The tectospinal tract (TST) originates in the deep layers of the superior colliculus. In the present study, we analyzed the corticotectal projections from two motor cortical areas, namely the premotor cortex (PM) and the primary motor cortex (M1) in eight macaque monkeys subjected to either a cortical lesion of the hand area in M1 (n = 4) or Parkinson’s disease-like symptoms PD (n = 4). A subgroup of monkeys with cortical lesion was subjected to anti-Nogo-A antibody treatment whereas all PD monkeys were transplanted with Autologous Neural Cell Ecosystems (ANCEs). The anterograde tracer BDA was used to label the axonal boutons both en passant and terminaux in the ipsilateral superior colliculus. Individual axonal boutons were charted in the different layers of the superior colliculus. In intact animals, we previously observed that corticotectal projections were denser when originating from PM than from M1. In the present M1 lesioned monkeys, as compared to intact ones the corticotectal projection originating from PM was decreased when treated with anti-Nogo-A antibody but not in untreated monkeys. In PD-like symptoms’ monkeys, on the other hand, there was no consistent change affecting the corticotectal projection as compared to intact monkeys. The present pilot study overall suggests that the corticotectal projection is less affected by M1 lesion or PD symptoms than the corticoreticular projection previously reported in the same animals.

Ultrastructural and optogenetic dissection of V1 corticotectal terminal synaptic properties.

The superior colliculus (SC) is a major site of sensorimotor integration in which sensory inputs are processed to initiate appropriate motor responses. Projections from the primary visual cortex (V1) to the SC have been shown to exert a substantial influence on visually induced behavior, including "freezing." However, it is unclear how V1 corticotectal terminals affect SC circuits to mediate these effects. To investigate this, we used anatomical and optogenetic techniques to examine the synaptic properties of V1 corticotectal terminals. Electron microscopy revealed that V1 corticotectal terminals labeled by anterograde transport primarily synapse (93%) on dendrites that do not contain gamma aminobutyric acid (GABA). This preference was confirmed using optogenetic techniques to photoactivate V1 corticotectal terminals in slices of the SC maintained in vitro. In a mouse line in which GABAergic SC interneurons express green fluorescent protein (GFP), few GFP-labeled cells (11%) responded to activation of corticotectal terminals. In contrast, 67% of non-GABAergic cells responded to activation of V1 corticotectal terminals. Biocytin-labeling of recorded neurons revealed that wide-field vertical (WFV) and non-WFV cells were activated by V1 corticotectal inputs. However, WFV cells were activated in the most uniform manner; 85% of these cells responded with excitatory postsynaptic potentials (EPSPs) that maintained stable amplitudes when activated with light trains at 1-20 Hz. In contrast, in the majority of non-WFV cells, the amplitude of evoked EPSPs varied across trials. Our results suggest that V1 corticotectal projections may initiate freezing behavior via uniform activation of the WFV cells, which project to the pulvinar nucleus.

Cortical projections to the superior colliculus in grey squirrels (Sciurus carolinensis).

The superior colliculus is an important midbrain structure involved with integrating information from varying sensory modalities and sending motor signals to produce orienting movements towards environmental stimuli. Because of this role, the superior colliculus receives a multitude of sensory inputs from a wide variety of subcortical and cortical structures. Proportionately, the superior colliculus of grey squirrels is among the largest in size of all studied mammals, suggesting the importance of this structure in the behavioural characteristics of grey squirrels. Yet, our understanding of the connections of the superior colliculus in grey squirrels is lacking, especially with respect to possible cortical influences. In this study, we placed anatomical tracer injections within the medial aspect of the superior colliculus of five grey squirrels (Sciurus carolinensis) and analysed the areal distribution of corticotectal projecting cells in flattened cortex. V1 projections to the superior colliculus were studied in two additional animals. Our results indicate that the superior colliculus receives cortical projections from visual, higher order somatosensory, and higher order auditory regions, as well as limbic, retrosplenial and anterior cingulate cortex. Few, if any, corticotectal projections originate from primary motor, primary somatosensory or parietal cortical regions. This distribution of inputs is similar to the distribution of inputs described in other rodents such as rats and mice, yet the lack of inputs from primary somatosensory and motor cortex is features of corticotectal inputs more similar to those observed in tree shrews and primates, possibly reflecting a behavioural shift from somatosensory (vibrissae) to visual navigation.

Ipsilateral corticotectal projections from the primary, premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study.

The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non-human primates, previous studies reported that cortical projections to the superior colliculus (SC) originated from the premotor cortex (PM) and the primary motor cortex, whereas no projection originated from the supplementary motor area (SMA). The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n=9). The anterograde tracer biotinylated dextran amine was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral SC. The data confirmed the presence of strong corticotectal projections from the PM. A new observation was that strong corticotectal projections were also found to originate from the SMA (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or SMAs. The corticotectal projection from each motor area was directed mainly to the deep layer of the SC, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non-primary motor areas are in position to influence the preparation and planning of voluntary movements.

A quantitative comparison of the hemispheric, areal, and laminar origins of sensory and motor cortical projections to the superior colliculus of the cat.

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a substantial projection. Conversely, only one area of the auditory orienting system, the auditory field of the anterior ectosylvian sulcus (fAES), and no area involved in somatosensory orienting, shows significant corticotectal inputs. Although small relative to visual inputs, the projection from the fAES is of particular interest, as it represents the only bilateral cortical input to the SC. This detailed, quantitative study allows for comparison across modalities in an animal that serves as a useful model for both auditory and visual perception. Moreover, the differences in patterns of corticotectal projections between modalities inform the ways in which orienting systems are modulated by cortical feedback. J. Comp. Neurol. 524:2623-2642, 2016. © 2016 Wiley Periodicals, Inc.

Sensory Cortical Control of a Visually Induced Arrest Behavior via Corticotectal Projections

Innate defense behaviors (IDBs) evoked by threatening sensory stimuli are essential for animal survival. Although subcortical circuits are implicated in IDBs, it remains largely unclear whether sensory cortex modulates IDBs and what the underlying neural pathways are. Here, we show that optogenetic silencing of corticotectal projections from layer 5 (L5) of the mouse primary visual cortex (V1) to the superior colliculus (SC) significantly reduces an SC-dependent innate behavior (i.e., temporary suspension of locomotion upon a sudden flash of light as short as milliseconds). Surprisingly, optogenetic activation of SC-projecting neurons in V1 or their axon terminals in SC sufficiently elicits the behavior, in contrast to other major L5 corticofugal projections. Thus, via the same corticofugal projection, visual cortex not only modulates the light-induced arrest behavior, but also can directly drive the behavior. Our results suggest that sensory cortex may play a previously unrecognized role in the top-down initiation of sensory-motor behaviors.

Distribution of cortical neurons projecting to the superior colliculus in macaque monkeys.

To better reveal the pattern of corticotectal projections to the superficial layers of the superior colliculus (SC), we made a total of ten retrograde tracer injections into the SC of three macaque monkeys (Macaca mulatta). The majority of these injections were in the superficial layers of the SC, which process visual information. To isolate inputs to the purely visual layers in the superficial SC from those inputs to the motor and multisensory layers deeper in the SC, two injections were placed to include the intermediate and deep layers of the SC. In another case, an injection was placed in the medial pulvinar, a nucleus not known to be strongly connected with visual cortex, to identify possible projections from tracer spread past the lateral boundary of the SC. Four conclusions are supported by the results: 1) all early visual areas of cortex, including V1, V2, V3, and the middle temporal area, project to the superficial layers of the SC; 2) with the possible exception of the frontal eye field, few areas of cortex outside of the early visual areas project to the superficial SC, although many do, however, project to the intermediate and deep layers of the SC; 3) roughly matching retinotopy is conserved in the projections of visual areas to the SC; and 4) the projections from different visual areas are similarly dense, although projections from early visual areas appear somewhat denser than those of higher order visual areas in macaque cortex.

Cortical projections to the superior colliculus in tree shrews (Tupaia belangeri).

The visuomotor functions of the superior colliculus depend not only on direct inputs from the retina, but also on inputs from neocortex. As mammals vary in the areal organization of neocortex, and in the organization of the number of visual and visuomotor areas, patterns of corticotectal projections vary. Primates in particular have a large number of visual areas projecting to the superior colliculus. As tree shrews are close relatives of primates, and they are also highly visual, we studied the distribution of cortical neurons projecting to the superior colliculus by injecting anatomical tracers into the colliculus. Since projections from visuotopically organized visual areas are expected to match the visuotopy of the superior colliculus, injections at different retinotopic locations in the superior colliculus provide information about the locations and organization of topographic areas in extrastriate cortex. Small injections in the superior colliculus labeled neurons in locations within areas 17 (V1) and 18 (V2) that are consistent with the known topography of these areas and the superior colliculus. In addition, the separate locations of clusters of labeled cells in temporal visual cortex provide evidence for five or more topographically organized areas. Injections that included deeper layers of the superior colliculus also labeled neurons in medial frontal cortex, likely in premotor cortex. Only occasional labeled neurons were observed in somatosensory or auditory cortex. Regardless of tracer injection location, we found that, unlike primates, a substantial projection to the superior colliculus from posterior parietal cortex is not a characteristic of tree shrews.

The protomap is propagated to cortical plate neurons through an Eomes -dependent intermediate map

The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a "protomap" in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The "intermediate map" in the SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 → Eomes → Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism.

Asymmetric N-cadherin expression results in synapse dysfunction, synapse elimination, and axon retraction in cultured mouse neurons.

Synapse elimination and pruning of axon collaterals are crucial developmental events in the refinement of neuronal circuits. While a control of synapse formation by adhesion molecules is well established, the involvement of adhesion molecules in developmental synapse loss is poorly characterized. To investigate the consequences of mis-match expression of a homophilic synaptic adhesion molecule, we analysed an asymmetric, exclusively postsynaptic expression of N-cadherin. This was induced by transfecting individual neurons in cultures of N-cadherin knockout mouse neurons with a N-cadherin expression vector. 2 days after transfection, patch-clamp analysis of AMPA receptor-mediated miniature postsynaptic currents revealed an impaired synaptic function without a reduction in the number of presynaptic vesicle clusters. Long-term asymmetric expression of N-cadherin for 8 days subsequently led to synapse elimination as indicated by a loss of colocalization of presynaptic vesicles and postsynaptic PSD95 protein. We further studied long-term asymmetric N-cadherin expression by conditional, Cre-induced knockout of N-cadherin in individual neurons in cultures of N-cadherin expressing cortical mouse neurons. This resulted in a strong retraction of axonal processes in individual neurons that lacked N-cadherin protein. Moreover, an in vivo asymmetric expression of N-cadherin in the developmentally transient cortico-tectal projection was indicated by in-situ hybridization with layer V neurons lacking N-cadherin expression. Thus, mis-match expression of N-cadherin might contribute to selective synaptic connectivity.

Projections to the Superior Colliculus From Inferior Parietal, Ventral Premotor, and Ventrolateral Prefrontal Areas Involved in Controlling Goal-Directed Hand Actions in the Macaque

We found that the macaque inferior parietal (PFG and anterior intraparietal [AIP]), ventral premotor (F5p and F5a), and ventrolateral prefrontal (rostral 46vc and intermediate 12r) areas forming a network involved in controlling purposeful hand actions ("lateral grasping network") are a source of corticotectal projections. Based on injections of anterograde tracers at the cortical level, the results showed that all these areas displayed relatively dense projections to the intermediate and deep gray layers of the ipsilateral superior colliculus (SC) and to the ventrally adjacent mesencephalic reticular formation. In the SC, the labeling tended to be richer in the lateral part along almost the entire rostro-caudal extent, that is, in regions controlling microsaccades and downward gaze shifts and hosting arm-related neurons and neurons modulated by the contact of the hand with the target. These projections could represent a descending motor pathway for controlling proximo-distal arm synergies. Furthermore, they could broadcast to the SC information related to hand action goals and object affordances extraction and selection. This information could be used in the SC for controlling orienting behavior (gaze and reaching movements) to the targets of object-oriented actions and for the eye-hand coordination necessary for appropriate hand-object interactions.

Cortical projections to the superior colliculus in prosimian galagos (Otolemur garnetti)

The superior colliculus (SC) is a key structure within the extrageniculate pathway of visual information to cortex and is highly involved in visuomotor functions. Previous studies in anthropoid primates have shown that superficial layers of the SC receive direct inputs from various visual cortical areas such as V1, V2, and middle temporal (MT), while deeper layers receive direct inputs from visuomotor cortical areas within the posterior parietal cortex and the frontal eye fields. Very little is known, however, about the corticotectal projections in prosimian primates. In the current study we investigated the sources of cortical inputs to the SC in prosimian galagos (Otolemur garnetti) using retrograde anatomical tracers placed into the SC. The superficial layers of the SC in galagos received the majority of their inputs from early visual areas and visual areas within the MT complex. Yet, surprisingly, MT itself had relatively few corticotectal projections. Deeper layers of the SC received direct projections from visuomotor areas including the posterior parietal cortex and premotor cortex. However, relatively few corticotectal projections originated within the frontal eye fields. While prosimian galagos resemble other primates in having early visual areas project to the superficial layers of the SC, with higher visuomotor regions projecting to deeper layers, the results suggest that MT and frontal eye field projections to the SC were sparse in early primates, remained sparse in present-day prosimian primates, and became more pronounced in anthropoid primates.

A role for ephrin‐As in maintaining topographic organization in register across interconnected central visual pathways

The retina sends spatially ordered visual information to the superior colliculus (SC) directly and indirectly via the thalamus and primary visual cortex (V1). Gradients of Ephs and ephrins are present in all of these regions, and have been shown to be involved in establishing topography of at least some of these interconnected visual pathways. Studies in ephrin-A knockout mice show that abnormal retinotectal termination zones (TZs) are present in a majority of mice lacking (-/-) ephrin-A2 (57%), and ephrin-A2 and -A5 (89%). A similar but seemingly less disordered pattern is detected in the retina-to-dorsal lateral geniculate nucleus (dLGN) and dLGN-to-V1 projections. Here we analyse the dLGN-to-V1 and V1-to-SC projections in ephrin-A(-/-) mice to determine the extent to which topographic errors are transmitted across synaptic relays. Fluorescent tracers were injected into V1 of wild-type (WT), ephrin-A2(-/-) or ephrin-A2A5(-/-) mice. We examined the number, location and size of anterograde TZs in SC, and mapped the distribution of retrogradely labelled neurons in dLGN. Compared with WT and ephrin-A2(-/-) mice, the volume of individual TZs in the SC was smaller in ephrin-A2A5(-/-) mice (P = 0.002). Single V1 injections labelled two foci of dLGN neurons in 70%, and two SC TZs in 80% of ephrin-A2A5(-/-) mice. Abnormalities in one or other of the projections were detected in 10% of ephrin-A2(-/-) mice. Importantly, there was no consistent correspondence between the organization of geniculocortical and corticotectal projections in either genotype, suggesting a role for ephrin-As in maintaining topographic organization in register across multiple interconnected central visual pathways.

Evolutionary evaluation of reciprocity of connections in the turtle tectofugal visual system

In two turtle species—Emys orbicularis and Testudo horsfieldi—by the method of anterograde and retrograde traicing at the light and electron microscopy level, the existence is proven of direct descending projections from the thalamic nucleus of the tectofugal visual system n. rotunds (Rot) to the optic tectum. After injection of tracers into Rot alone and into Rot with involvement of the tectothalamic tract (Trtth), occasional labeled fibers with varicosities and terminals are revealed predominantly in the deep sublayers of SGFS of the rostral optic tectum, while in the lower amount—in other tectal layers. After the tracer injections into the optic tectum, a few retrogradely labeled neurons were found mainly in the Rot ventral parts and within Trtth. Their localization coincides with that of GABA-immunoreactive cells. Electron microscopy showed the existence of many retrogradely labeled dendrites throughout the whole Rot; a few labeled cell bodies were also present there, some of them being also GABA-immunoreactive. These results allow us to conclude about the existence of reciprocal connections between the optic tectum and Rot in turtles, these connections being able to affect processing of visual information in tectum. We suggest that reciprocity of tectothalamic connections might be the ancestral feature of the vertebrate brain; in the course of amniote evolution the functional significance of this feature can be decreased and even lost in parallel with a rise of the role of direct corticotectal projections.

Mixing Modalities Is More Than Meets the Eye Alone. Focus on: “Multisensory Versus Unisensory Integration: Contrasting Modes in the Superior Colliculus”

The processes and mechanisms whereby individual neurons integrate and compute converging synaptic information from multiple sources remains as one of the more intriguing issues in experimental cellular and computational neuroscience. Nowhere are these issues more clearly relevant to understanding a tractable set of integrative neurophysiological and behavioral questions than in the realm of multi-sensory integration. In this issue of the Journal of Neurophysiology (p. 3193–3205), Alvarado and colleagues make a significant contribution to this field by carefully evaluating the interactive responses of neurons in the superior colliculus in response to paired stimuli arising from either the same sensory modality or across modalities. Most interestingly, the same neuron will often respond to unimodal paired stimuli with simple linear (or even sublinear) interactions while responding to cross-modal inputs in a supralinear fashion. Although the phenomenon of multisensory super-additivity, particularly when the modality specific stimuli are weak, has been described previously (Meredith and Stein 1983; Stanford et al. 2005), heretofore there has not been a systematic experimental exploration of the nature of the differences in the computational processes for individual neurons for within and between modality processing. The experiments by Alvarado et al. were performed by recording the evoked spike activity from individual deep layer superior collicular neurons in anesthetized adult cats in response to individual modality visual, auditory, and combined stimuli both within and between sensory modalities. The results are derived from just under 100 neurons of which about half were multisensory and half were visual unisensory. Interestingly, the responses of both unisensory- and multisensory stimuli to within-modal stimuli (e.g., 2 visual stimuli) were similar in their lack of super-additive responses, whereas the same multisensory neurons responded to cross-modal inputs in a generally super-additive fashion. These experiments directly address one of the central questions of multi-sensory integration— do the integrative properties that facilitate multimodal responses of neurons and thus the behavioral salience of multimodal sensory cues arise from particular intrinsic properties of the individual multisensory neurons or from the local network properties in which the multisensory neurons are imbedded? The authors’ argue for the latter hypothesis—that is, if there were fundamentally different intrinsic properties of multisensory neurons, their integration of multiple modality inputs that are super-additive should extend to their integration of unisensory inputs. This was not the case. Moreover, this finding was also consonant with their observation that additive or sub-additive integration of multiple inputs by unisensory neurons was more similar to integration of multiple inputs by multisensory neurons than was the integration of unisensory versus multisensory inputs by multisensory neurons. The authors’ study provides new rich data for enhancing simulations of multisensory integration by individual neurons imbedded within synaptic networks. Even more intriguing are the experiments suggested by the results. Although much of the leading research into multisensory processing has been carried out in the intact brain where the spiking responses of individual neurons, particularly in the superior colliculus can be studied in response to stimuli that access the sensory apparatus, there is a growing appreciation for the importance of complementing these studies by probing the biophysical and synaptic properties of these cells and the synaptic networks in which they are contained. Armed with evidence that there are differences in individual neuron’s responses to unimodal and cross-modal stimuli, there should be opportunities for new efforts to uncover exactly how these processes are instantiated at the circuit level. Such studies should benefit from the application of modern cellular imaging, multiple electrode recording and refined subcellular neuroanatomical analysis of the sites of various inputs to multisensory collicular neurons (Skaliora et al. ). These studies will still have substantial challenges as it is well established that the descending cortico-tectal projections play a major role in the multisensory properties of deep collicular neurons. However, the intriguing results of Alvarado et al. make the case for the emergence of additional supraadditive properties within the collicular circuitry, motivating additional work on the integrative properties of this fascinating structure that has a major role in sensory processing in the entire lineage of vertebrate species.

Functional specialization in non-primary auditory cortex of the cat: Areal and laminar contributions to sound localization

The purpose of this study is to: (1) examine the relative contributions of the 13 acoustically-responsive regions of the cerebral cortex to sound localization; (2) examine the laminar contributions to spatial localization behavior for each of the cortical areas identified to be critical for accurately determining the position of a sound source; and (3) synthesize the findings from sound localization studies and the underlying corticocortical and corticotectal connections to develop a processing system for sound localization information within and between the cerebral cortex and the superior colliculus. First, we examined performance on a sound localization task before, during, and after unilateral or bilateral reversible cooling deactivation of each region of acoustically-responsive cortex. Overall, unilateral deactivation of primary auditory cortex and the dorsal zone (AI/DZ), the posterior auditory field (PAF), or the auditory field of the anterior ectosylvian sulcus (AES) yielded profound sound localization deficits in the contralateral field. Bilateral deactivations of the same regions yielded bilateral sound localization deficits. Second, graded cooling of AI/DZ or PAF showed that deactivation of only the superficial layers was required to elicit sound localization deficits. However, graded cooling of AES revealed that cooling of the superficial layers alone does not cause significant sound localization deficits. Profound deficits were identified only when cooling extended through the full thickness of AES cortex. Therefore, we propose that the superficial layers of AI/DZ or PAF and the deeper layers of AES are necessary for determining the precise location of a sound source. Finally, when these results are combined with data on corticocortical and corticotectal projections, we propose that signals processed in the superficial layers of AI, DZ, or PAF feed forward to the auditory field of AES. In turn, neurons in the deeper layers of AES project to the intermediate and deeper layers of the superior colliculus. Therefore, we propose that sound localization signals processed in primary and non-primary auditory cortex are transmitted to the superior colliculus by means of the auditory field of the AES.

Cortical Efferent Control of Subcortical Sensory Neurons by Synaptic Disinhibition

A long-standing hypothesis predicts that pyramidal neurons of the cerebral cortex control the influx of sensory information at the level of primary sensory representations areas. Yet little is known about the cellular mechanisms governing selective attention to behaviorally relevant objects in space. Neurons in the superficial layers of the superior colliculus are notably involved in this process, and they are directly targeted by retinal and cortical afferents. To study long-term and short-term effects of the visual cortex (VC) on subcortical visual neurons we established an in vitro model of the developing cortico-tectal projection. To this end, cortical explants expressing Green Fluorescent Protein were allowed to form connections with non-labeled dissociated tectal neurons. The presence of VC explants led to an enhancement of tectal activity by 2 mechanisms. First, glutamatergic input was increased. Second, intrinsic GABAergic inhibition was suppressed. The latter effect was shown to be acute and mediated through postsynaptic metabotropic glutamate receptor activation, G-protein acitivity, and endocannabinoid receptor activation. The VC-induced disinhibition was readily reversed by application of an mGluR antagonist. However, high-frequency activation of the glutamatergic cortico-tectal input turned the labile disinhibition into a persistent suppression of inhibition.

Thalamic connections of the auditory cortex in marmoset monkeys: Core and medial belt regions

In this study and its companion, the cortical and subcortical connections of the medial belt region of the marmoset monkey auditory cortex were compared with the core region. The main objective was to document anatomical features that account for functional differences observed between areas. Injections of retrograde and bi-directional anatomical tracers targeted two core areas (A1 and R), and two medial belt areas (rostromedial [RM] and caudomedial [CM]). Topographically distinct patterns of connections were revealed among subdivisions of the medial geniculate complex (MGC) and multisensory thalamic nuclei, including the suprageniculate (Sg), limitans (Lim), medial pulvinar (PM), and posterior nucleus (Po). The dominant thalamic projection to the CM was the anterior dorsal division (MGad) of the MGC, whereas the posterior dorsal division (MGpd) targeted RM. CM also had substantial input from multisensory nuclei, especially the magnocellular division (MGm) of the MGC. RM had weak multisensory connections. Corticotectal projections of both RM and CM targeted the dorsomedial quadrant of the inferior colliculus, whereas the CM projection also included a pericentral extension around the ventromedial and lateral portion of the central nucleus. Areas A1 and R were characterized by focal topographic connections within the ventral division (MGv) of the MGC, reflecting the tonotopic organization of both core areas. The results indicate that parallel subcortical pathways target the core and medial belt regions and that RM and CM represent functionally distinct areas within the medial belt auditory cortex.