Query: rat visual cortex

title: Functional Local Input to Layer 5 Pyramidal Neurons in the Rat Visual Cortex.
abstract: Pyramidal neurons in layer 5 of the neocortex can be differentiated into 3 cell subtypes: 1) short regular spiking (SH) 2) tall regular spiking (TR) and 3) tall burst spiking (TB) based on their morphological and electrophysiological properties. We characterized the functional excitatory local input to these 3 cell subtypes in rat primary visual cortex using laser scanning photostimulation. Although all cell types received significant input from all cortical layers, SH neurons received stronger input from layer 4 and weaker input from layer 5 than did tall pyramidal cells. However, the laminar input to the 2 populations of tall pyramidal cells was indistinguishable. Simultaneous paired recording were then used to calculate a correlation probability (CP) to infer the proportion of shared input based on the occurrence of simultaneous synaptic potentials. Tall pairs of matched type had significantly higher CPs compared with unmatched pairs, suggesting that subpopulations of layer 4, 5, and 6 neurons preferentially connect to each tall cell type. Hence, this study shows that unconnected but matching pairs of tall pyramidal neurons, but not short pyramidal neurons, receive functional input from different interconnected networks within layers 4, 5, and 6.

title: Early depolarizing GABA controls critical period plasticity in the rat visual cortex
abstract: Hyperpolarizing and inhibitory GABA regulates critical periods for plasticity in sensory cortices. Here we examine the role of early, depolarizing GABA in the control of plasticity mechanisms. We report that brief interference with depolarizing GABA during early development prolonged critical period plasticity in visual cortical circuits without affecting the overall development of the visual system. The effects on plasticity were accompanied by dampened inhibitory neurotransmission, downregulation of brain derived neurotrophic factor (BDNF) expression and reduced density of extracellular matrix perineuronal nets. Early interference with depolarizing GABA decreased perinatal BDNF signaling, and a pharmacological increase of BDNF signaling during GABA interference rescued the effects on plasticity and its regulators later in life. We conclude that depolarizing GABA exerts a long lasting, selective modulation of plasticity of cortical circuits by a strong crosstalk with BDNF.

title: Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex
abstract: Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre and post synaptic proteins (Synapsin, Synaptophysin, PSD 95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter individual variability that are different for the four proteins and include a stage during early development <1 year) when only Gephyrin has high inter individual variability. We also found that pre and post synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the 1 year or 2 of life. A multidimensional analysis (principle component analysis) showed that most of the variance was captured by the sum of the four synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic.

title: Developmental Switch of the Serotonergic Role in the Induction of Synaptic Long term Potentiation in the Rat Visual Cortex
abstract: Synaptic long term potentiation (LTP) and long term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5 hydroxytryptamine, 5 HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks) However, in adult rats, the increase in 5 HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5 HT on the induction of LTP in the visual cortex obtained from 3 to 10 week old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta burst stimulation (TBS) in 3 and 5 week old rats, then declined to the baseline level with aging to 10 weeks. Whereas 5 HT inhibited the induction of LTP in 5 week old rats, it reinstated the induction of N methyl D aspartate receptor (NMDA) dependent LTP in 8 and 10 week old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5 HT at 8 weeks of age was mediated by the activation of 5 HT2 receptors, but not by the activation of either 5 HT1A or 5 HT3 receptors. These results suggested that the effect of 5 HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

title: Interactions between two propagating waves in rat visual cortex
abstract: Sensory evoked propagating waves are frequently observed in sensory cortex. However, it is largely unknown how an evoked propagating wave affects the activity evoked by subsequent sensory inputs, or how two propagating waves interact when evoked by simultaneous sensory inputs. Using voltage sensitive dye imaging, we investigated the interactions between two evoked waves in rat visual cortex, and the spatiotemporal patterns of depolarization in the neuronal population due to wave to wave interactions. We have found that visually evoked propagating waves have a refractory period of about 300 ms, within which the response to a subsequent visual stimulus is suppressed. Simultaneous presentation of two visual stimuli at different locations can evoke two waves propagating toward each other, and these two waves fuse. Fusion significantly shortens the latency and half width of the response, leading to changes in the spatial profile of evoked population activity. The visually evoked propagating wave may also be suppressed by a preceding spontaneous wave. The refractory period following a propagating wave and the fusion between two waves may contribute to visual sensory processing by modifying the spatiotemporal profile of population neuronal activity evoked by sensory events.

title: Activation of Rho GTPases Triggers Structural Remodeling and Functional Plasticity in the Adult Rat Visual Cortex
abstract: A classical example of age dependent plasticity is ocular dominance (OD) plasticity, triggered by monocular deprivation (MD) Sensitivity of cortical circuits to a brief period of MD is maximal in juvenile animals and downregulated in adult age. It remains unclear whether a reduced potential for morphological remodeling underlies this downregulation of physiological plasticity in adulthood. Here we have tested whether stimulation of structural rearrangements is effective in promoting experience dependent plasticity in adult age. We have exploited a bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1) that regulates actin dynamics and structure of neuronal processes via a persistent activation of Rho GTPases. Injection of CNF1 into the adult rat visual cortex triggered a long lasting activation of the Rho GTPase Rac1, with a consequent increase in spine density and length in pyramidal neurons. Adult rats treated with CNF1, but not controls, showed an OD shift toward the open eye after MD. CNF1 mediated OD plasticity was selectively attributable to the enhancement of open eye responses, whereas closed eye inputs were unaffected. This effect correlated with an increased density of geniculocortical terminals in layer IV of monocularly deprived, CNF1 treated rats. Thus, Rho GTPase activation reinstates OD plasticity in the adult cortex via the potentiation of more active inputs from the open eye. These data establish a direct link between structural remodeling and functional plasticity and demonstrate a role for Rho GTPases in brain plasticity in vivo. The plasticizing effects of Rho GTPase activation may be exploited to promote brain repair.

title: NMDA Receptor Hypofunction Phase Couples Independent g Oscillations in the Rat Visual Cortex
abstract: Hallucinations, a hallmark of psychosis, can be induced by the psychotomimetic N methyl D aspartic acid (NMDA) receptor antagonists, ketamine and phencyclidine (PCP) and are associated with hypersynchronization in the g frequency band, but it is unknown how reduced interneuron activation associated with NMDA receptor hypofunction can cause hypersynchronization or distorted perception. Low frequency g oscillations (LFg) and high frequency g oscillations (HFg) serve different aspects of perception. In this study, we test whether ketamine and PCP affect the interactions between HFg and LFg in the rat visual cortex in vitro. In slices of the rat visual cortex, kainate and carbachol induced LFg ~34 Hz at 32degC) in layer V and HFg ~54 Hz) in layer III of the same cortical column. In controls, HFg and LFg were independent, and pyramidal neurons recorded in layer III were entrained by HFg, but not by LFg. Sub anesthetic concentrations of ketamine selectively decelerated HFg by 22 Hz (EC50=2.7 mM) to match the frequency of LFg in layer V. This caused phase coupling of the two g oscillations, increased spatial coherence in layer III, and entrained the firing of layer III pyramidal neurons by LFg in layer V. PCP similarly decelerated HFg by 22 Hz (EC50=0.16 mM) causing cross layer phase coupling of g oscillations. Selective NMDA receptor antagonism, selective NR2B subunit containing receptor antagonism, and reduced D serine levels caused a similar selective deceleration of HFg, whereas increasing NMDA receptor activation through exogenous NMDA, D serine, or mGluR group 1 agonism selectively accelerated HFg. The NMDA receptor hypofunction induced phase coupling of the normally independent g generating networks is likely to cause abnormal cross layer interactions, which may distort perceptions due to aberrant matching of top down information with bottom up information. If decelerated HFg and subsequent cross layer synchronization also underlie pathological psychosis, acceleration of HFg could be the target for improved antipsychotic therapy.

title: High frequency gamma oscillations coexist with low frequency gamma oscillations in the rat visual cortex in vitro
abstract: Synchronization of neuronal activity in the visual cortex at low (30 70 Hz) and high gamma band frequencies 70 Hz) has been associated with distinct visual processes, but mechanisms underlying high frequency gamma oscillations remain unknown. In rat visual cortex slices, kainate and carbachol induce high frequency gamma oscillations (fast g; peak frequency 80 Hz at 37degC) that can coexist with low frequency gamma oscillations (slow g; peak frequency 50 Hz at 37degC) in the same column. Current source density analysis showed that fast g was associated with rhythmic current sink source sequences in layer III and slow g with rhythmic current sink source sequences in layer V. Fast g and slow g were not phase locked. Slow g power fluctuations were unrelated to fast g power fluctuations, but were modulated by the phase of theta (3 8 Hz) oscillations generated in the deep layers. Fast g was spatially less coherent than slow g. Fast g and slow g were dependent on g aminobutyric acid (GABA)A receptors, a amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid (AMPA) receptors and gap junctions, their frequencies were reduced by thiopental and were weakly dependent on cycle amplitude. Fast g and slow g power were differentially modulated by thiopental and adenosine A1 receptor blockade, and their frequencies were differentially modulated by N methyl d aspartate (NMDA) receptors, GluK1 subunit containing receptors and persistent sodium currents. Our data indicate that fast g and slow g both depend on and are paced by recurrent inhibition, but have distinct pharmacological modulation profiles. The independent co existence of fast g and slow g allows parallel processing of distinct aspects of vision and visual perception. The visual cortex slice provides a novel in vitro model to study cortical high frequency gamma oscillations.

title: "Slow Activity Transients" in Infant Rat Visual Cortex:A Spreading Synchronous Oscillation Patterned by Retinal Waves
abstract: A primary feature of the preterm infant electroencephalogram is the presence of large infra slow potentials containing rapid oscillations called slow activity transients (SATs) Such activity has not been described in animal models, and their generative mechanisms are unknown. Here we use direct current and multisite extracellular, as well as whole cell, recording in vivo to demonstrate the existence of regularly repeating SATs in the visual cortex of infant rats before eye opening. Present only in absence of anesthesia, SATs at postnatal day 10 11 were identifiable as a separate group of long duration ~10 s) events that consisted of large >1 mV) negative local field potentials produced by the summation of multiple bursts of rapid oscillatory activity (15 30 Hz) SATs synchronized the vast majority of neuronal activity (87% in the visual cortex before eye opening. Enucleation eliminated SATs, and their duration, interevent interval, and sub burst structure matched those of phase III retinal waves recorded in vitro. Retinal waves, however, lacked rapid oscillations, suggesting that they arise centrally. Multielectrode recordings showed that SATs spread horizontally in cortex and synchronize activity at coactive locales via the rapid oscillations. SATs were clearly different from ongoing cortical activity, which was observable as a separate class of short bursts from postnatal day 9. Together, our data suggest that, in vivo, early cortical activity is primarily determined by peripheral inputs retinal waves in visual cortex that provide excitatory input, and by thalamocortical circuitry, which transforms this input to beta oscillations. We propose that the synchronous oscillations of SATs participate in the formation of visual circuitry.

title: Blockade of different muscarinic receptor subtypes changes the equilibrium between excitation and inhibition in rat visual cortex
abstract: We have shown that cortical acetylcholine modulates the balance between excitation and inhibition evoked in layer 5 pyramidal neurons of rat visual cortex [Lucas Meunier E, Monier C, Amar M, Baux G, Fregnac Y, Fossier P (2009) Cereb Cortex 19:2411 2427] Our aim is now to establish a functional basis for the role of the different types of muscarinic receptors (MRs) on glutamate fibers and on GABAergic interneurons and to analyse their contribution to the modulation of excitation inhibition balance in the rat visual cortex. To ascertain that there was a basis for our functional study, we first checked for the presence of the various MR subtypes by single cell RT PCR and immunolabeling experiments. Then, recording the composite responses in layer 5 pyramidal neurons to layer 1 2 stimulation (which also recruits cholinergic fibers) in the presence of specific antagonists of the different types of MR allowed us to determine their modulatory role. We show that the specific blockade of the widely distributed M1R (with the mamba toxin, MT7) induced a significant increase in the excitatory conductance without modifying the inhibitory conductance, pointing to a localization of M1R on glutamatergic neurons where their activation would decrease the release of glutamate. From our functional results, M2/M4Rs appear to be located on glutamatergic neurons afferent to the recorded layer 5 pyramidal neuron and they decrease glutamate release. The extended distribution of M4Rs in the cortex compared to the restricted distribution of M2R (layers 3 5) is in favour of a major role as a modulator of M4R. The selective antagonist of M3Rs, 4 DAMP, decreased the inhibitory conductance, showing that activated M3Rs increase the release of GABA and thus are located on GABAergic interneurons. The activation of the different types of MRs located either on glutamatergic neurons or on GABAergic interneurons converges to reinforce the dominance of inhibitory inputs thus decreasing the excitability of layer 5 pyramidal neurons.