Increased excitability of cortical neurons induced by associative learning: an ex vivo study

Abstract In adult mice, classical conditioning in which whisker stimulation is paired with an electric shock to the tail results in a decrease in the frequency of head movements, induces expansion of the cortical representation of stimulated vibrissae and enhances inhibitory synaptic interactions within the 'trained' barrels. We investigated whether such a simple associative learning paradigm also induced changes in neuronal excitability. Using whole-cell recordings from ex vivo slices of the barrel cortex we found that layer IV excitatory cells located in the cortical representation of the 'trained' row of vibrissae had a higher frequency of spikes recorded at threshold potential than neurons from the 'untrained' row and than cells from control animals. Additionally, excitatory cells within the 'trained' barrels were characterized by increased gain of the input-output function, lower amplitudes of fast after-hyperpolarization and decreased effect of blocking of BK channels by iberiotoxin. These findings provide new insight into the possible mechanism for enhanced intrinsic excitability of layer IV excitatory neurons. In contrast, the fast spiking inhibitory cells recorded in the same barrels did not change their intrinsic excitability after the conditioning procedure. The increased excitability of excitatory neurons within the 'trained' barrels may represent the counterpart of homeostatic plasticity, which parallels enhanced synaptic inhibition described previously. Together, the two mechanisms would contribute to increase the input selectivity within the conditioned cortical network

20 Hz rhythm of activity in visual system of perceiving cat.

Abstract. Cats attended to either visual or acoustic moving stimuli in order to perceive the location of their disappearance, which signaled reward in left or right foodwell. The analysis of concomitant electroencephalograms revealed an elevation of the 20 Hz band in the Fourier spectra of activity of respective visual and auditory projection cortices. These oscillations appeared only on the trials that ended with a successful response. With use of directed transfer functions we were able to show that during the visual task, the 20 Hz frequency was propagated from the spot of appearance along the visual cortex, as well as towards the lateral geniculate nucleus

Visual classification of X and Y perigeniculate neurons of the cat. Exp Brain Res 101:307–313

Abstract The spike activity of perigeniculate cells evoked by small light spots flashing along the axes of their receptive fields was recorded and presented in response planes. This method allowed the investigated neurons to be grouped into two classes characterized by (1) large receptive fields and phasic-like responses and (2) small fields and tonic responses. The latency measurements for stimulation of the optic chiasma and visual cortex revealed that the cells from the first group are excited by fast, Y fibers and the second by slow, X axons. The spatial tuning curves of the second harmonic component, as measured from the responses of the cells from the two groups for slowly moving square gratings, are also different. We conclude that the X and Y systems of the visual pathway are segregated at the level of the perigeniculate nucleus

Coupling of beta and gamma activity in cortico-thalamic system of cats attending to visual stimuli.

WE have previously shown that local ®eld potentials (LFPs) recorded in the lateral geniculate nucleus (LGN) and primary visual cortex (VCx) of the cat contain signi®cantly more beta frequency activity when the animal attends to visual than to auditory stimuli. In the present study we utilised data from the same experiments to calculate the cross-correlation between envelopes of ®ltered beta (16±24 Hz) and gamma (30±45 Hz) oscillatory signals recorded at the same sites. Correlation values obtained from visual trials were signi®cantly higher than those calculated for the auditory task. This observation was typical in those LGN and VCx recording sites which corresponded to the central representation of the visual ®eld. The cross-correlation function peaked within a 20 ms time window from the centre of the cross-correlogram. These ®ndings support the hypothesis that beta activity provides an excitatory background for the appearance of oscillations in the gamma band

Cholinergic and Noradrenergic Modulation of Corticothalamic Synaptic Input From Layer 6 to the Posteromedial Thalamic Nucleus in the Rat

Cholinergic and noradrenergic neuromodulation of the synaptic transmission from cortical layer 6 of the primary somatosensory cortex to neurons in the posteromedial thalamic nucleus (PoM) was studied using an in vitro slice preparation from young rats. Cholinergic agonist carbachol substantially decreased the amplitudes of consecutive excitatory postsynaptic potentials (EPSPs) evoked by a 20 Hz five pulse train. The decreased amplitude effect was counteracted by a parallel increase of synaptic frequency-dependent facilitation. We found this modulation to be mediated by muscarinic acetylcholine receptors. In the presence of carbachol the amplitudes of the postsynaptic potentials showed a higher trial-to-trial coefficient of variation (CV), which suggested a presynaptic site of action for the modulation. To substantiate this finding, we measured the failure rate of the excitatory postsynaptic currents in PoM cells evoked by "pseudominimal" stimulation of corticothalamic input. A higher failure-rate in the presence of carbachol indicated decreased probability of transmitter release at the synapse. Activation of the noradrenergic modulatory system that was mimicked by application of norepinephrine did not affect the amplitude of the first EPSP evoked in the five-pulse train, but later EPSPs were diminished. This indicated a decrease of the synaptic frequency-dependent facilitation. Treatment with noradrenergic alpha-2 agonist clonidine, alpha-1 agonist phenylephrine, or beta-receptor agonist isoproterenol showed that the modulation may partly rely on alpha-2 adrenergic receptors. CV analysis did not suggest a presynaptic action of norepinephrine. We conclude that cholinergic and noradrenergic modulation act as different variable dynamic controls for the corticothalamic mechanism of the frequency-dependent facilitation in PoM.Funding Agencies|European Union Regional Development Fund through the Foundation for Polish Science; National Science CenterNational Science Centre, Poland [2013/08/W/NZ4/00691]</p

The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention.

Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation

Forced Remyelination Promotes Axon Regeneration in a Rat Model of Spinal Cord Injury

Spinal cord injuries result in the loss of motor and sensory functions controlled by neurons located at the site of the lesion and below. We hypothesized that experimentally enhanced remyelination supports axon preservation and/or growth in the total spinal cord transection in rats. Multifocal demyelination was induced by injection of ethidium bromide (EB), either at the time of transection or twice during transection and at 5 days post-injury. We demonstrated that the number of oligodendrocyte progenitor cells (OPCs) significantly increased 14 days after demyelination. Most OPCs differentiated into mature oligodendrocytes by 60–90 dpi in double-EB-injected rats; however, most axons were remyelinated by Schwann cells. A significant number of axons passed the injury epicenter and entered the distant segments of the spinal cord in the double-EB-injected rats. Moreover, some serotoninergic fibers, not detected in control animals, grew caudally through the injury site. Behavioral tests performed at 60–90 dpi revealed significant improvement in locomotor function recovery in double-EB-injected rats, which was impaired by the blockade of serotonin receptors, confirming the important role of restored serotonergic fibers in functional recovery. Our findings indicate that enhanced remyelination per se, without substantial inhibition of glial scar formation, is an important component of spinal cord injury regeneration

Unusual Quadrupedal Locomotion in Rat during Recovery from Lumbar Spinal Blockade of 5-HT7 Receptors

Coordination of four-limb movements during quadrupedal locomotion is controlled by supraspinal monoaminergic descending pathways, among which serotoninergic ones play a crucial role. Here we investigated the locomotor pattern during recovery from blockade of 5-HT7 or 5-HT2A receptors after intrathecal application of SB269970 or cyproheptadine in adult rats with chronic intrathecal cannula implanted in the lumbar spinal cord. The interlimb coordination was investigated based on electromyographic activity recorded from selected fore- and hindlimb muscles during rat locomotion on a treadmill. In the time of recovery after hindlimb transient paralysis, we noticed a presence of an unusual pattern of quadrupedal locomotion characterized by a doubling of forelimb stepping in relation to unaffected hindlimb stepping (2FL-1HL) after blockade of 5-HT7 receptors but not after blockade of 5-HT2A receptors. The 2FL-1HL pattern, although transient, was observed as a stable form of fore-hindlimb coupling during quadrupedal locomotion. We suggest that modulation of the 5-HT7 receptors on interneurons located in lamina VII with ascending projections to the forelimb spinal network can be responsible for the 2FL-1HL locomotor pattern. In support, our immunohistochemical analysis of the lumbar spinal cord demonstrated the presence of the 5-HT7 immunoreactive cells in the lamina VII, which were rarely 5-HT2A immunoreactive

Beta activity increases in the primary visual cortex during attention trials.

<p>A. Stimulus-driven paradigm (cat B, Cx 17/1, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145379#pone.0145379.t001" target="_blank">Table 1</a>). Left: mean FFT spectra obtained from all correct trials during the three experimental days after the behavioral criterion was reached. The visual (gray) and auditory (black) means were obtained by averaging respectively 820 and 760 spectra of 1.28 s long data epochs (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145379#sec002" target="_blank">Methods</a> for details). Right: comparison of the mean spectrum from the correct visual trials (gray; same as in the left panel) with the mean FFT from 90 epochs from incorrect trials (black). B. Anticipatory paradigm (cat E, Cx 17/2). The recorded signals were subjected to the same analysis as in A. Means were obtained from 748 and 765 spectra for correspondingly correct visual and correct auditory trials, and from 320 spectra for incorrect visual trials. In A and B, the shading around the FFT spectra indicates the SEM. The lines above the horizontal axes denote the frequencies at which significant differences were found between the spectra from the correct visual and auditory (left) or correct and incorrect visual (right) trials (Student's t-tests with FDR correction for multiple comparisons, see the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145379#sec002" target="_blank">Methods</a> section; P ≤ 0.05). An example of filtered (16–24 Hz) beta signals recorded from cat B at the beginning of two correct stimulus-driven visual and auditory trials (right and left panel, respectively) performed on the second day after the cat reached the behavioral criterion. The consecutive horizontal lines in each panel represent a continuous signal. The vertical lines separate the final part of the signal corresponding to the inter-trial period preceding stimulus onset and the start of the stimulus presentation during the trial.</p

Experimental paradigms.

<p>A. In the stimulus-driven attention paradigm, the visual and auditory trials started with the cue stimulus (a light spot or a modulated noise delivered from a loudspeaker) that moved in front of the cage for 10–20 s. The spot was switched off in front of one of the doors or the noise stopped along the side wall. The transparent screen was lifted 2 s later, and the cat was allowed to open the indicated door for a food reward. Visual and auditory trials (n = 12–20 for each) were randomly intermingled. The cage was fully closed during the experiment by a removable cover (not shown). With the exception of the two semi-translucent doors on the front, the rest of the cage was opaque (the cat’s entire body was drawn only for graphical demonstration). B. During the anticipatory paradigm, the cue was either a short (1 s) diffuse flash on both doors or a white noise delivered from the front loudspeaker. The animal then anticipated the target for 8–14 s with no stimulation present, after which a small spot of light or white noise from the side loudspeaker was delivered. C. The upper trace shows a typical LFP recording in which the beta activity can be traced by eye; the filtered beta band of this record is shown beneath the LFP signal. See the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145379#sec002" target="_blank">Methods</a> section for details.</p