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The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. Whether this diversity applies to other brain cells, such as the glial cells astrocytes, remains unexplored. Using optogenetics and two-photon functional imaging in the adult mouse neocortex, we here reveal that parvalbumin- and somatostatin-expressing interneurons, two key interneuron classes in the brain, differentially signal to astrocytes inducing weak and robust GABA B receptor-mediated Ca 2+ elevations, respectively. Furthermore, the astrocyte response depresses upon parvalbumin interneuron repetitive stimulations and potentiates upon somatostatin interneuron repetitive stimulations, revealing a distinguished astrocyte plasticity. Remarkably, the potentiated response crucially depends on the neuropeptide somatostatin, released by somatostatin interneurons, which activates somatostatin receptors at astrocytic processes. Our study unveils, in the living brain, a hitherto unidentified signaling specificity between interneuron subtypes and astrocytes opening a new perspective into the role of astrocytes as non-neuronal components of inhibitory circuits. Interneurons in the neocortex have functional and morphological subtypes. Here, Mariotti and colleagues show that activation of parvalbumin-expressing interneurons evokes depressing calcium responses in astrocytes while somatostatin-expressing interneurons evoke potentiating astrocytic responses.

All-optical methods for imaging and manipulating brain networks with high spatial resolution are fundamental to study how neuronal ensembles drive behavior. Stimulation of neuronal ensembles using two-photon holographic techniques requires high-sensitivity actuators to avoid photodamage and heating. Moreover, two-photon-excitable opsins should be insensitive to light at wavelengths used for imaging. To achieve this goal, we developed a novel soma-targeted variant of the large-conductance blue-light-sensitive opsin CoChR (stCoChR). In the mouse cortex in vivo, we combined holographic two-photon stimulation of stCoChR with an amplified laser tuned at the opsin absorption peak and two-photon imaging of the red-shifted indicator jRCaMP1a. Compared to previously characterized blue-light-sensitive soma-targeted opsins in vivo, stCoChR allowed neuronal stimulation with more than 10-fold lower average power and no spectral crosstalk. The combination of stCoChR, tuned amplified laser stimulation, and red-shifted functional indicators promises to be a powerful tool for large-scale interrogation of neural networks in the intact brain.

Imaging neuronal activity with high and homogeneous spatial resolution across the field-of-view (FOV) and limited invasiveness in deep brain regions is fundamental for the progress of neuroscience, yet is a major technical challenge. We achieved this goal by correcting optical aberrations in gradient index lens-based ultrathin (≤500 µm) microendoscopes using aspheric microlenses generated through 3D-microprinting. Corrected microendoscopes had extended FOV ( eFOV ) with homogeneous spatial resolution for two-photon fluorescence imaging and required no modification of the optical set-up. Synthetic calcium imaging data showed that, compared to uncorrected endoscopes, eFOV -microendoscopes led to improved signal-to-noise ratio and more precise evaluation of correlated neuronal activity. We experimentally validated these predictions in awake head-fixed mice. Moreover, using eFOV- microendoscopes we demonstrated cell-specific encoding of behavioral state-dependent information in distributed functional subnetworks in a primary somatosensory thalamic nucleus. eFOV- microendoscopes are, therefore, small-cross-section ready-to-use tools for deep two-photon functional imaging with unprecedentedly high and homogeneous spatial resolution.

Social animals live and move through spaces shaped by the presence, motion and sensory cues of multiple other individuals 1 – 6 . Neural activity in the hippocampus is known to reflect spatial behaviour 7 – 9 yet its study is lacking in such dynamic group settings, which are ubiquitous in natural environments. Here we studied hippocampal activity in groups of bats engaged in collective spatial behaviour. We find that, under spontaneous conditions, a robust spatial structure emerges at the group level whereby behaviour is anchored to specific locations, movement patterns and individual social preferences. Using wireless electrophysiological recordings from both stationary and flying bats, we find that many hippocampal neurons are tuned to key features of group dynamics. These include the presence or absence of a conspecific, but not typically of an object, at landing sites, shared spatial locations, individual identities and sensory signals that are broadcasted in the group setting. Finally, using wireless calcium imaging, we find that social responses are anatomically distributed and robustly represented at the population level. Combined, our findings reveal that hippocampal activity contains a rich representation of naturally emerging spatial behaviours in animal groups that could in turn support the complex feat of collective behaviour. In bats engaged in spontaneous collective spatial behaviour, a robust spatial structure emerges at the group level whereby behaviour is anchored to specific locations, movement patterns and individual social preferences, and many hippocampal neurons are tuned to key features of group dynamics.

Neural activity in the hippocampus is known to reflect how animals move through an environment 1 , 2 . Although navigational behaviour may show considerable stability 3 – 6 , the tuning stability of individual hippocampal neurons remains unclear 7 – 12 . Here we used wireless calcium imaging to longitudinally monitor the activity of dorsal CA1 hippocampal neurons in freely flying bats performing highly reproducible flights in a familiar environment. We find that both the participation and the spatial selectivity of most neurons remain stable over days and weeks. We also find that apparent changes in tuning can be largely attributed to variations in the flight behaviour of the bats. Finally, we show that bats navigating in the same environment under different room lighting conditions (lights on versus lights off) exhibit substantial changes in flight behaviour that can give the illusion of neuronal instability. However, when similar flight paths are compared across conditions, the stability of the hippocampal code persists. Taken together, we show that the underlying hippocampal code is highly stable over days and across contexts if behaviour is taken into account. The hippocampal code in freely flying bats is highly stable over days and across contexts if behaviour is taken into account.

Imaging neuronal activity with high and homogeneous spatial resolution across the field-of-view (FOV) and limited invasiveness in deep brain regions is fundamental for the progress of neuroscience, yet is a major technical challenge. We achieved this goal by correcting optical aberrations in gradient index lens-based ultrathin microendoscopes using aspheric microlenses generated through 3D-microprinting. Corrected microendoscopes had extended FOV (eFOV) with homogeneous spatial resolution for two-photon fluorescence imaging and required no modification of the optical set-up. Synthetic calcium imaging data showed that, compared to uncorrected endoscopes, eFOV-microendoscopes led to improved signal-to-noise ratio and more precise evaluation of correlated neuronal activity. We experimentally validated these predictions in awake head-fixed mice. Moreover, using eFOV-microendoscopes we demonstrated cell-specific encoding of behavioral state-dependent information in distributed functional subnetworks in a primary somatosensory thalamic nucleus. eFOV-microendoscopes are, therefore, small-cross-section ready-to-use tools for deep two-photon functional imaging with unprecedentedly high and homogeneous spatial resolution. Competing Interest Statement The authors have declared no competing interest.

Here, we report on a patient with a 625 kb duplication in Xp22.12, detected by array comparative genomic hybridization (CGH). The duplicated region contains only one gene, RPS6KA3, that results in partial duplication. The same duplication was present in his mother and his maternal uncle. This partial duplication inhibits the RPS6KA3 expression, mimicking the effect of loss-of-function mutations associated with Coffin-Lowry syndrome (CLS). The phenotype of the patient here presented is not fully evocative of this syndrome because he does not present some of the facial, digital and skeletal abnormalities that are considered the main diagnostic features of CLS. This case is one of the few examples where RPS6KA3 mutations are associated with a non-specific X-linked mental retardation.

The early identification of pre-lingual deafness is necessary to minimize the consequences of hearing impairment on the future communication skills of a baby. According to the most recent international guidelines the deafness diagnosis must occur before the age of three months and the prosthetic-rehabilitative treatment with a traditional hearing aid should start within the first six months. When a Cochlear implant becomes necessary, the treatment should start between the age of 12 months and 18 months. The only way to diagnose the problem early is the implementation of universal neonatal audiological screening programs. Transient evoked otoacoustic emissions (TEOAE) is the most adequate test because it's accurate, economic and of simple execution. Automatic auditory brainstem response (AABR) is necessary to identify patients with auditory neuropathy but it is also important to reduce the number of false-positives.The 20-30% of infant hearing impairment is represented by progressive or late-onset hearing loss (HL) so it's also necessary to establish an audiological follow up program, especially in infants at risk. From November 2005 all neonates born in the University hospital of Pisa undergo newborn hearing screening. From 2008 the screening program follows the guidelines for the execution of the audiological screening in Tuscany which have been formulated by our group according to the 2007 JCIH Position Statement and adaptated to our regional reality by a multidisciplinary effort. From November 2005 to April 2009 8113 neonates born in the Neonatal Unit of Santa Chiara Hospital (Pisa) have undergone newborn hearing screening. 7621 neonates (93.9%) without risk factors executed only the TEOAE test. 492 (6.1%) neonates had audiological risk factors and thus underwent TEOAE and AABR. 84 patients (1,04%) failed both TEOAE and AABR tests. 78 of them underwent further investigations. 44 patients resulted falsepositives (the 0,54% of the screened newborns). 34 neonates (4,2 ‰) had a final diagnosis of hearing impairment. 8 patients (0.99 ‰) had unilateral hearing loss (HL). 26 patients (3,2 ‰) had bilateral hearing impairment. In our screening program the percentage of false-positives was quite low (0.54%) while the incidence of bilateral HL (3.2 ‰) is a little higher than that found in literature reports. In most of our patients premature birth or neonatal suffering represent the main cause of HL.