Potentiation of sensory responses in ventrobasal thalamus in vivo via selective modulation of mGlu1 receptors with a positive allosteric modulator.

Metabotropic glutamate subtype 1 (mGlu1) receptor is thought to play a role in synaptic responses in thalamic relay nuclei. The aim of this study was to evaluate the positive allosteric modulator (PAM) Ro67-4853 as a tool to modulate thalamic mGlu1 receptors on single thalamic neurones in vivo. Ro67-4853, applied by iontophoresis onto ventrobasal thalamus neurones of urethane-anaesthetised rats, selectively enhanced responses to the agonist (S)-3,5-dihydroxy-phenylglycine (DHPG), an effect consistent with mGlu1 potentiation. The PAM was also able to enhance maintained responses to 10 Hz trains of sensory stimulation of the vibrissae, but had little effect on responses to single sensory stimuli. Thus Ro67-4853 appears to be a highly selective tool that can be useful in investigating how mGlu1 receptor potentiation can alter neural processing in vivo. Our results show the importance of mGlu1 in sensory processing and attention mechanisms at the thalamic level and suggest that positive modulation of mGlu1 receptors might be a useful mechanism for enhancing cognitive and attentional processes

Responses of primate LGN cells to moving stimuli involve a constant background modulation by feedback from area MT

The feedback connections from the cortical motion area middle temporal (MT), to layer 6 of the primary visual cortex (V1), have the capacity to drive a cascaded feedback influence from the layer 6 cortico-geniculate cells back to the lateral geniculate nucleus (LGN) relay cells. This introduces the possibility of a re-entrant motion signal affecting the relay of the retinal input through the LGN to the visual cortex. The question is whether the response of LGN cells to moving stimuli involves a component derived from this feedback. By producing a reversible focal pharmacological block of the activity of an MT direction column we show the presence of such an influence from MT on the responses of magno, parvo and koniocellular cells in the macaque LGN. The pattern of effect in the LGN reflects the direction bias of the MT location inactivated. This suggests a moving stimulus is captured by iterative interactions in the circuit formed by visual cortical areas and visual thalamus

Spontaneous Local Gamma Oscillation Selectively Enhances Neural Network Responsiveness

Synchronized oscillation is very commonly observed in many neuronal systems and might play an important role in the response properties of the system. We have studied how the spontaneous oscillatory activity affects the responsiveness of a neuronal network, using a neural network model of the visual cortex built from Hodgkin-Huxley type excitatory (E-) and inhibitory (I-) neurons. When the isotropic local E-I and I-E synaptic connections were sufficiently strong, the network commonly generated gamma frequency oscillatory firing patterns in response to random feed-forward (FF) input spikes. This spontaneous oscillatory network activity injects a periodic local current that could amplify a weak synaptic input and enhance the network's responsiveness. When E-E connections were added, we found that the strength of oscillation can be modulated by varying the FF input strength without any changes in single neuron properties or interneuron connectivity. The response modulation is proportional to the oscillation strength, which leads to self-regulation such that the cortical network selectively amplifies various FF inputs according to its strength, without requiring any adaptation mechanism. We show that this selective cortical amplification is controlled by E-E cell interactions. We also found that this response amplification is spatially localized, which suggests that the responsiveness modulation may also be spatially selective. This suggests a generalized mechanism by which neural oscillatory activity can enhance the selectivity of a neural network to FF inputs

Feedback Enhances Feedforward Figure-Ground Segmentation by Changing Firing Mode

In the visual cortex, feedback projections are conjectured to be crucial in figure-ground segregation. However, the precise function of feedback herein is unclear. Here we tested a hypothetical model of reentrant feedback. We used a previous developed 2-layered feedforwardspiking network that is able to segregate figure from ground and included feedback connections. Our computer model data show that without feedback, neurons respond with regular low-frequency (∼9 Hz) bursting to a figure-ground stimulus. After including feedback the firing pattern changed into a regular (tonic) spiking pattern. In this state, we found an extra enhancement of figure responses and a further suppression of background responses resulting in a stronger figure-ground signal. Such push-pull effect was confirmed by comparing the figure-ground responses withthe responses to a homogenous texture. We propose that feedback controlsfigure-ground segregation by influencing the neural firing patterns of feedforward projecting neurons

Assessment of 180° rotation of the choroid as a novel surgical treatment for age-related macular degeneration.

PURPOSE: Our objective was to examine the feasibility of rotating choriocapillaris, Bruch's membrane (BM), and retinal pigment epithelium (RPE) through 180° on a vascular pedicle and to assess revascularization and tissue preservation postoperatively. Such an approach could be used in the treatment of age-related macular degeneration where there is focal disease at the macula with healthy tissues located peripherally. METHODS: Successful surgery was performed in six rhesus macaque monkeys, which have a very similar choroidal blood supply to humans. After inducing a retinal detachment, the recurrent branch of the long posterior ciliary artery was used as a pedicle around which a graft stretching to the temporal equator was rotated. Retina was reattached over the rotated graft and eyes were followed up for up to 6 months with repeated angiography and optical coherence tomography (OCT). The morphology of retinal cells and BM were assessed by immunohistochemistry and electron microscopy. RESULTS: Revascularization of the choroid was limited, with reestablishment of drainage to the vortex veins seen in only one case. There was a secondary loss of the RPE and outer retina evident on histological analysis three months after surgery. The underlying BM however remained intact. CONCLUSIONS: Pedicled choroidal rotation surgery is technically feasible in vivo with intraoperative control of bleeding. However, lack of graft revascularization with the technique in its current form leads to neuroretinal and RPE tissue loss, and graft shrinkage. We found no evidence that rotational grafts are likely to improve the outcomes presently achieved with free graft techniques