Rodents' visual gamma as a biomarker of pathological neural conditions.

Neural gamma oscillations (indicatively 30-100 Hz) are ubiquitous: they are associated with a broad range of functions in multiple cortical areas and across many animal species. Experimental and computational works established gamma rhythms as a global emergent property of neuronal networks generated by the balanced and coordinated interaction of excitation and inhibition. Coherently, gamma activity is strongly influenced by the alterations of synaptic dynamics which are often associated with pathological neural dysfunctions. We argue therefore that these oscillations are an optimal biomarker for probing the mechanism of cortical dysfunctions. Gamma oscillations are also highly sensitive to external stimuli in sensory cortices, especially the primary visual cortex (V1), where the stimulus dependence of gamma oscillations has been thoroughly investigated. Gamma manipulation by visual stimuli tuning is particularly easy in rodents, which have become a standard animal model for investigating the effects of network alterations on gamma oscillations. Overall, gamma in the rodents' visual cortex offers an accessible probe on dysfunctional information processing in pathological conditions. Beyond vision-related dysfunctions, alterations of gamma oscillations in rodents were indeed also reported in neural deficits such as migraine, epilepsy and neurodegenerative or neuropsychiatric conditions such as Alzheimer's, schizophrenia and autism spectrum disorders. Altogether, the connections between visual cortical gamma activity and physio-pathological conditions in rodent models underscore the potential of gamma oscillations as markers of neuronal (dys)functioning.

Predicting party switching through machine learning and open data.

Parliament dynamics might seem erratic at times. Predicting future voting patterns could support policy design based on the simulation of voting scenarios. The availability of open data on legislative activities and machine learning tools might enable such prediction. In our paper, we provide evidence for this statement by developing an algorithm able to predict party switching in the Italian Parliament with over 70% accuracy up to two months in advance. The analysis was based on voting data from the XVII (2013-2018) and XVIII (2018-2022) Italian legislature. We found party switchers exhibited higher participation in secret ballots and showed a progressive decrease in coherence with their party's majority votes up to two months before the actual switch. These results show how machine learning combined with political open data can support predicting and understanding political dynamics.

Molecular changes underlying decay of sensory responses and enhanced seizure propensity in peritumoral neurons.

BACKGROUND: Glioblastoma growth impacts on the structure and physiology of peritumoral neuronal networks, altering the activity of pyramidal neurons which drives further tumor progression. It is therefore of paramount importance to identify glioma-induced changes in pyramidal neurons, since they represent a key therapeutic target. METHODS: We longitudinal monitored visual evoked potentials after the orthotopic implant of murine glioma cells into the mouse occipital cortex. With laser microdissection, we analyzed layer II-III pyramidal neurons molecular profile and with local field potentials recordings we evaluated the propensity to seizures in glioma-bearing animals with respect to control mice. RESULTS: We determine the time course of neuronal dysfunction of glioma-bearing mice and we identify a symptomatic stage, based on the decay of visual response. At that time point, we microdissect layer II-III pyramidal neurons and evaluate the expression of a panel of genes involved in synaptic transmission and neuronal excitability. Compared to the control group, peritumoral neurons show a decrease in the expression of the SNARE complex gene SNAP25 and the alpha1 subunit of the GABA-A receptor. No significant changes are detected in glutamatergic (ie, AMPA or NMDA receptor subunit) markers. Further reduction of GABA-A signaling by delivery of a benzodiazepine inverse agonist, DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) precipitates seizures in 2 mouse models of tumor-bearing mice. CONCLUSIONS: These studies reveal novel molecular changes that occur in the principal cells of the tumor-adjacent zone. These modifications may be therapeutically targeted to ameliorate patients' quality of life.

Disruption of layer-specific visual processing in a model of focal neocortical epilepsy.

The epileptic brain is the result of a sequence of events transforming normal neuronal populations into hyperexcitable networks supporting recurrent seizure generation. These modifications are known to induce fundamental alterations of circuit function and, ultimately, of behavior. However, how hyperexcitability affects information processing in cortical sensory circuits is not yet fully understood. Here, we investigated interlaminar alterations in sensory processing of the visual cortex in a mouse model of focal epilepsy. We found three main circuit dynamics alterations in epileptic mice: (i) a spreading of visual contrast-driven gamma modulation across layers, (ii) an increase in firing rate that is layer-unspecific for excitatory units and localized in infragranular layers for inhibitory neurons, and (iii) a strong and contrast-dependent locking of firing units to network activity. Altogether, our data show that epileptic circuits display a functional disruption of layer-specific organization of visual sensory processing, which could account for visual dysfunction observed in epileptic subjects. Understanding these mechanisms paves the way to circuital therapeutic interventions for epilepsy.

Environmental enrichment counteracts the effects of glioma in primary visual cortex.

Experience-dependent neuronal changes and brain plasticity occur throughout life as animals adapt to their environment. Structural, morphological, and cellular modifications promoted by exposure to environmental enrichment (EE) have been reported to improve neuronal functions, increase hippocampal neurogenesis, ameliorate memory tasks and cognitive performance, and have beneficial effects on several brain diseases, including cancer. We specifically addressed the role of the EE in counteracting neuronal dysfunction in mice bearing glioma in the primary visual cortex. By recording spontaneous and evoked currents with patch clamp techniques in acute slices obtained from standard and enriched-housed mice, we found that the presence of glioma globally reduced the excitatory and inhibitory transmissions in the peritumoral area. The exposure to an enriched environment counteracts the tumor-mediated depression of both excitatory and inhibitory neuronal activities, with a more pronounced impact on evoked transmission. The effect of EE on glioma was also associated with reduced tumor cell proliferation. These results elucidate the impact of EE on excitatory and inhibitory neurotransmission of the primary visual cortex in control and glioma-bearing mice.

Synaptic alterations in visual cortex reshape contrast-dependent gamma oscillations and inhibition-excitation ratio in a genetic mouse model of migraine.

BACKGROUND: Migraine affects a significant fraction of the world population, yet its etiology is not completely understood. In vitro results highlighted thalamocortical and intra-cortical glutamatergic synaptic gain-of-function associated with a monogenic form of migraine (familial-hemiplegic-migraine-type-1: FHM1). However, how these alterations reverberate on cortical activity remains unclear. As altered responsivity to visual stimuli and abnormal processing of visual sensory information are common hallmarks of migraine, herein we investigated the effects of FHM1-driven synaptic alterations in the visual cortex of awake mice. METHODS: We recorded extracellular field potentials from the primary visual cortex (V1) of head-fixed awake FHM1 knock-in (n = 12) and wild type (n = 12) mice in response to square-wave gratings with different visual contrasts. Additionally, we reproduced in silico the obtained experimental results with a novel spiking neurons network model of mouse V1, by implementing in the model both the synaptic alterations characterizing the FHM1 genetic mouse model adopted. RESULTS: FHM1 mice displayed similar amplitude but slower temporal evolution of visual evoked potentials. Visual contrast stimuli induced a lower increase of multi-unit activity in FHM1 mice, while the amount of information content about contrast level remained, however, similar to WT. Spectral analysis of the local field potentials revealed an increase in the ß/low γ range of WT mice following the abrupt reversal of contrast gratings. Such frequency range transitioned to the high γ range in FHM1 mice. Despite this change in the encoding channel, these oscillations preserved the amount of information conveyed about visual contrast. The computational model showed how these network effects may arise from a combination of changes in thalamocortical and intra-cortical synaptic transmission, with the former inducing a lower cortical activity and the latter inducing the higher frequencies É£ oscillations. CONCLUSIONS: Contrast-driven É£ modulation in V1 activity occurs at a much higher frequency in FHM1. This is likely to play a role in the altered processing of visual information. Computational studies suggest that this shift is specifically due to enhanced cortical excitatory transmission. Our network model can help to shed light on the relationship between cellular and network levels of migraine neural alterations.

Narrow and Broad γ Bands Process Complementary Visual Information in Mouse Primary Visual Cortex.

γ Band plays a key role in the encoding of visual features in the primary visual cortex (V1). In rodents V1 two ranges within the γ band are sensitive to contrast: a broad γ band (BB) increasing with contrast, and a narrow γ band (NB), peaking at ∼60 Hz, decreasing with contrast. The functional roles of the two bands and the neural circuits originating them are not completely clear yet. Here, we show, combining experimental and simulated data, that in mice V1 (1) BB carries information about high contrast and NB about low contrast; (2) BB modulation depends on excitatory-inhibitory interplay in the cortex, while NB modulation is because of entrainment to the thalamic drive. In awake mice presented with alternating gratings, NB power progressively decreased from low to intermediate levels of contrast where it reached a plateau. Conversely, BB power was constant across low levels of contrast, but it progressively increased from intermediate to high levels of contrast. Furthermore, BB response was stronger immediately after contrast reversal, while the opposite held for NB. These complementary modulations were reproduced by a recurrent excitatory-inhibitory leaky integrate-and-fire network provided that the thalamic inputs were composed of a sustained and a periodic component having complementary sensitivity ranges. These results show that in rodents the thalamic-driven NB plays a specific key role in encoding visual contrast. Moreover, we propose a simple and effective network model of response to visual stimuli in rodents that might help in investigating network dysfunctions of pathologic visual information processing.

Ultrasound Stimulations Induce Prolonged Depolarization and Fast Action Potentials in Leech Neurons.

Objective: Ultrasound (US) stimulation carries the promise of a selective, reversible, and non-invasive modulation of neural activity without the need for genetic manipulation of neural structures. However, the mechanisms of US-induced generation of action potentials (APs) are still unclear. Methods: Here we address this issue by analyzing intracellularly recorded responses of leech nociceptive neurons to controlled delivery of US. Results: US induced a depolarization linearly accumulating in time and outlasting the duration of the stimulation. Spiking activity was reliably induced for an optimal US intensity range. Moreover, we found that APs induced by US differ in smaller amplitude and faster repolarization from those induced by electrical stimulation in the same cell but display the same repolarization rate. Conclusions: These results shed light on the mechanism by which spikes are induced by US and pave the way for designing more efficient US stimulation patterns.