Vishal Bharmauria

Fluoxetine and serotonin facilitate attractive‐adaptation‐induced orientation plasticity in adult cat visual cortex

Neurons in V1 display orientation selectivity by responding optimally to a preferred orientation edge when it is presented within their receptive fields. Orientation plasticity in striate cortex occurs either by ocular deprivation or by imposition of a non‐preferred stimulus for several minutes. Adaptation of neurons to a non‐optimal orientation induces shifts of tuning curves towards the adapting orientation (attractive shift) or away from it (repulsive shift). Here, we investigated the effects of the neurotransmitter serotonin and antidepressant fluoxetine (a selective serotonin reuptake inhibitor) on the modulation of adaptation‐induced orientation plasticity. We show that serotonin and fluoxetine promote mostly attractive shifts. Attractive shifts augmented in magnitude towards adapter, whereas repulsive neurons reversed their behavior in the direction of the forced orientation. Furthermore, neurons which retained their original preferred orientation expressed plasticity by shifting their tuning curves after drug administration mostly towards adapter. Our data suggest a pre‐eminent role of fluoxetine by inducing and facilitating short‐term plasticity in V1.

Adaptation shifts preferred orientation of tuning curve in the mouse visual cortex.

In frontalized mammals it has been demonstrated that adaptation produces shift of the peak of the orientation tuning curve of neuron following frequent or lengthier presentation of a non-preferred stimulus. Depending on the duration of adaptation the shift is attractive (toward the adapter) or repulsive (away from the adapter). Mouse exhibits a salt-and-pepper cortical organization of orientation maps, hence this species may respond differently to adaptation. To examine this question, we determined the effect of twelve minutes of adaptation to one particular orientation on neuronal orientation tuning curves in V1 of anesthetized mice. Multi-unit activity of neurons in V1 was recorded in a conventional fashion. Cells were stimulated with sine-wave drifting gratings whose orientation tilted in steps. Results revealed that similarly to cats and monkeys, majority of cells shifted their optimal orientation in the direction of the adapter while a small proportion exhibited a repulsive shift. Moreover, initially untuned cells showing poor tuning curves reacted to adaptation by displaying sharp orientation selectivity. It seems that modification of the cellular property following adaptation is a general phenomenon observed in all mammals in spite of the different organization pattern of the visual cortex. This study is of pertinence to comprehend the mechanistic pathways of brain plasticity.

Comparative analysis of orientation maps in areas 17 and 18 of the cat primary visual cortex following adaptation

Object orientations in the visual field are columned into specific orientation domains in the primary visual cortex [area 17 (A17) and area 18 (A18)] of cats. At the single‐cell level, adapting A17 neurons to a non‐preferred orientation (adaptor) shifts their preferred orientation either towards the adaptor (attractive shift) or away from it (repulsive shift). As A17 and A18 are reciprocally connected, we sought to determine how changes in preferred orientations in A18 neurons are correlated with changes recorded in A17 anesthetised cats. To this end, we simultaneously traced populations of neurons in A17 and A18, using intrinsic optical imaging, before and after long (12 min) and short (3 min) adaptations. The comparison of A17 and A18 maps pre‐adaptation and post‐adaptation showed that variance in shift amplitudes is greater in A18 than A17 for short adaptations. Our results indicate a rapid reconfiguration of functional maps that may spread to many cortical areas.

Reprogramming of orientation columns in visual cortex: a domino effect

Cortical organization rests upon the fundamental principle that neurons sharing similar properties are co-located. In the visual cortex, neurons are organized into orientation columns. In a column, most neurons respond optimally to the same axis of an oriented edge, that is, the preferred orientation. This orientation selectivity is believed to be absolute in adulthood. However, in a fully mature brain, it has been established that neurons change their selectivity following sensory experience or visual adaptation. Here, we show that after applying an adapter away from the tested cells, neurons whose receptive fields were located remotely from the adapted site also exhibit a novel selectivity in spite of the fact that they were not adapted. These results indicate a robust reconfiguration and remapping of the orientation domains with respect to each other thus removing the possibility of an orientation hole in the new hypercolumn. These data suggest that orientation columns transcend anatomy, and are almost strictly functionally dynamic.

Synergistic activity between primary visual neurons.

Cortical microcircuitry plays a pivotal role in encoding sensory information reaching the cortex. However, the fundamental knowledge concerning the mechanisms that govern feature-encoding by these sub-networks is still sparse. Here, we show through multi-electrode recordings in V1 of conventionally prepared anesthetized cats, that an avalanche of synergistic neural activity occurs between functionally connected neurons in a cell-assembly in response to the presented stimulus. The results specifically show that once the reference neuron spikes in a connected neuron-pair, it facilitates the response of its companion (target) neuron for 50ms and, thereafter, the excitability of the target neuron declines. On the other hand, the functionally unconnected neurons do not facilitate each others activity within the 50-ms time-window. The added excitation (facilitation) of connected neurons is almost four times the responsiveness of unconnected neurons. This suggests that connectedness confers the added excitability to neurons; consequently leading to feature-encoding within the emergent 50-ms-period. Furthermore, the facilitation significantly decreases as a function of orientation selectivity spread.

Network-selectivity and stimulus-discrimination in the primary visual cortex: cell-assembly dynamics.

Visual neurons coordinate their responses in relation to the stimulus; however, the complex interplay between a stimulus and the functional dynamics of an assembly still eludes neuroscientists. To this aim, we recorded cell assemblies from multi‐electrodes in the primary visual cortex of anaesthetized cats in response to randomly presented sine‐wave drifting gratings whose orientation tilted in 22.5° steps. Cross‐correlograms revealed the functional connections at all the tested orientations. We show that a cell‐assembly discriminates between orientations by recruiting a ‘salient’ functional network at every presented orientation, wherein the connections and their strengths (peak‐probabilities in the cross‐correlogram) change from one orientation to another. Within these assemblies, closely tuned neurons exhibited increased connectivity and connection‐strengths compared with differently tuned neurons. Minimal connectivity between untuned neurons suggests the significance of neuronal selectivity in assemblies. This study reflects upon the dynamics of functional connectivity, and brings to the fore the importance of a ‘signature’ functional network in an assembly that is strictly related to a specific stimulus. It appears that an assembly is the major ‘functional unit’ of information processing in cortical circuits, rather than the individual neurons.

Stimulus-dependent augmented gamma oscillatory activity between the functionally connected cortical neurons in the primary visual cortex.

Neuronal assemblies typically synchronise within the gamma oscillatory band (30–80 Hz) and are fundamental to information processing. Despite numerous investigations, the exact mechanisms and origins of gamma oscillations are yet to be known. Here, through multiunit recordings in the primary visual cortex of cats, we show that the strength of gamma power (20–40 and 60–80 Hz) is significantly stronger between the functionally connected units than between the unconnected units within an assembly. Furthermore, there is increased frequency coherence in the gamma band between the connected units than between the unconnected units. Finally, the higher gamma rhythms (60–80 Hz) are mostly linked to the fast‐spiking neurons. These results led us to postulate that gamma oscillations are intrinsically generated between the connected units within cell assemblies (microcircuits) in relation to the stimulus within an emergent ‘50‐ms temporal window of opportunity’.

Modulation of functional connectivity following visual adaptation: Homeostasis in V1

Sensory neurons exhibit remarkable adaptability in acquiring new optimal selectivity to unfamiliar features when a new stimulus becomes prevalent in the environment. In conventionally prepared adult anesthetized cats, we used visual adaptation to change the preferred orientation selectivity in V1 neurons. Cortical circuits are dominated by complex and intricate connections between neurons. Cross-correlation of cellular spike-trains discloses the putative functional connection between two neurons. We sought to investigate changes in these links following a 12 min uninterrupted application of a specific, usually non-preferred, orientation. We report that visual adaptation, mimicking training, modulates the magnitude of crosscorrelograms suggesting that the strength of inter-neuronal relationships is modified. While individual cell-pairs exhibit changes in their response correlation strength, the average correlation of the recorded cell cluster remains unchanged. Hence, visual adaptation induces plastic changes that impact the connectivity between neurons.

Summation of connectivity strengths in the visual cortex reveals stability of neuronal microcircuits after plasticity

BackgroundWithin sensory systems, neurons are continuously affected by environmental stimulation. Recently, we showed that, on cell-pair basis, visual adaptation modulates the connectivity strength between similarly tuned neurons to orientation and we suggested that, on a larger scale, the connectivity strength between neurons forming sub-networks could be maintained after adaptation-induced-plasticity. In the present paper, based on the summation of the connectivity strengths, we sought to examine how, within cell-assemblies, functional connectivity is regulated during an exposure-based adaptation.ResultsUsing intrinsic optical imaging combined with electrophysiological recordings following the reconfiguration of the maps of the primary visual cortex by long stimulus exposure, we found that within functionally connected cells, the summed connectivity strengths remain almost equal although connections among individual pairs are modified. Neuronal selectivity appears to be strongly associated with neuronal connectivity in a “homeodynamic” manner which maintains the stability of cortical functional relationships after experience-dependent plasticity.ConclusionsOur results support the “homeostatic plasticity concept” giving new perspectives on how the summation in visual cortex leads to the stability within labile neuronal ensembles, depending on the newly acquired properties by neurons.

Comparative effects of adaptation on layers II-III and V-VI neurons in cat V1.

V1 is fundamentally grouped into columns that descend from layers II–III to V–VI. Neurons inherent to visual cortex are capable of adapting to changes in the incoming stimuli that drive the cortical plasticity. A principle feature called orientation selectivity can be altered by the presentation of non‐optimal stimulus called ‘adapter’. When triggered, LGN cells impinge upon layer IV and further relay the information to deeper layers via layers II–III. Using different adaptation protocols, neuronal plasticity can be investigated. Superficial neurons in area V1 are well acknowledged to exhibit attraction and repulsion by shifting their tuning peaks when challenged by a non‐optimal stimulus called ‘adapter’. Layers V–VI neurons in spite of partnering layers II–III neurons in cortical computation have not been explored simultaneously toward adaptation. We believe that adaptation not only affects cells specific to a layer but modifies the entire column. In this study, through simultaneous multiunit recordings in anesthetized cats using a multichannel depth electrode, we show for the first time how layers V–VI neurons (1000–1200 μm) along with layers II–III neurons (300–500 μm) exhibit plasticity in response to adaptation. Our results demonstrate that superficial and deeper layer neurons react synonymously toward adapter by exhibiting similar behavioral properties. The neurons displayed similar amplitude of shift and maintained equivalent sharpness of Gaussian tuning peaks before and the following adaptation. It appears that a similar mechanism, belonging to all layers, is responsible for the analog outcome of the neurons’ experience with adapter.