Comparison of LFP-Based and Spike-Based Spectro-Temporal Receptive Fields and Cross-Correlation in Cat Primary Auditory Cortex

Multi-electrode array recordings of spike and local field potential (LFP) activity were made from primary auditory cortex of 12 normal hearing, ketamine-anesthetized cats. We evaluated 259 spectro-temporal receptive fields (STRFs) and 492 frequency-tuning curves (FTCs) based on LFPs and spikes simultaneously recorded on the same electrode. We compared their characteristic frequency (CF) gradients and their cross-correlation distances. The CF gradient for spike-based FTCs was about twice that for 2–40 Hz-filtered LFP-based FTCs, indicating greatly reduced frequency selectivity for LFPs. We also present comparisons for LFPs band-pass filtered between 4–8 Hz, 8–16 Hz and 16–40 Hz, with spike-based STRFs, on the basis of their marginal frequency distributions. We find on average a significantly larger correlation between the spike based marginal frequency distributions and those based on the 16–40 Hz filtered LFP, compared to those based on the 4–8 Hz, 8–16 Hz and 2–40 Hz filtered LFP. This suggests greater frequency specificity for the 16–40 Hz LFPs compared to those of lower frequency content. For spontaneous LFP and spike activity we evaluated 1373 pair correlations for pairs with >200 spikes in 900 s per electrode. Peak correlation-coefficient space constants were similar for the 2–40 Hz filtered LFP (5.5 mm) and the 16–40 Hz LFP (7.4 mm), whereas for spike-pair correlations it was about half that, at 3.2 mm. Comparing spike-pairs with 2–40 Hz (and 16–40 Hz) LFP-pair correlations showed that about 16% (9%) of the variance in the spike-pair correlations could be explained from LFP-pair correlations recorded on the same electrodes within the same electrode array. This larger correlation distance combined with the reduced CF gradient and much broader frequency selectivity suggests that LFPs are not a substitute for spike activity in primary auditory cortex

Perinatal Asphyxia Affects Rat Auditory Processing: Implications for Auditory Perceptual Impairments in Neurodevelopmental Disorders

Perinatal asphyxia, a naturally and commonly occurring risk factor in birthing, represents one of the major causes of neonatal encephalopathy with long term consequences for infants. Here, degraded spectral and temporal responses to sounds were recorded from neurons in the primary auditory cortex (A1) of adult rats exposed to asphyxia at birth. Response onset latencies and durations were increased. Response amplitudes were reduced. Tuning curves were broader. Degraded successive-stimulus masking inhibitory mechanisms were associated with a reduced capability of neurons to follow higher-rate repetitive stimuli. The architecture of peripheral inner ear sensory epithelium was preserved, suggesting that recorded abnormalities can be of central origin. Some implications of these findings for the genesis of language perception deficits or for impaired language expression recorded in developmental disorders, such as autism spectrum disorders, contributed to by perinatal asphyxia, are discussed

Synaptic and circuit mechanisms promoting broadband transmission of olfactory stimulus dynamics

Sensory stimuli fluctuate on many timescales. However, short-term plasticity causes synapses to act as temporal filters, limiting the range of frequencies they can transmit. How synapses in vivo might transmit a range of frequencies in spite of short-term plasticity is poorly understood. The first synapse in the Drosophila olfactory system exhibits short-term depression, and yet can transmit broadband signals. Here we describe two mechanisms that broaden the frequency characteristics of this synapse. First, two distinct excitatory postsynaptic currents transmit signals on different timescales. Second, presynaptic inhibition dynamically updates synaptic properties to promote accurate transmission of signals across a wide range of frequencies. Inhibition is transient but grows slowly, and simulations show that these two features of inhibition promote broadband synaptic transmission. Dynamic inhibition is often thought to restrict the temporal patterns that a neuron responds to, but our results illustrate a different idea: inhibition can expand the bandwidth of neural coding

Multiparameter modalities for the study of patients in the setting of individualized medicine

The recent revolution in cancer genetics offers the promise of using genetic information to individualize patient treatment. In pancreatic cancer, numerous studies have described a genetic landscape characterized by a set of commonly mutated genes aggregated into core molecular pathways accompanied by numerous but infrequently mutated genes. Studies have also demonstrated significant intratumoral heterogeneity. Resistance against chemotherapeutic agents has also been attributed to difficulty of drug delivery through a rich stromal microenvironment. For these reasons, therapeutic development against pancreatic cancer has been challenging, and a number of promising agents have failed clinical trial testing. Personalized models have been studied as a tool for testing candidate drugs to select the most efficacious treatment. The patient-derived xenograft (PDX) is a well-established preclinical tool to improve the drug screening and development. The PDX model requires adequate tissue for transplantation, and failure is common. A recently described, innovative three-dimensional organoid culture platform can be exploited for genomic and functional studies at the level of the individual patient for personalized treatment approach. Organoid technology may fill the gap between cancer genetics and patient trials and allow personalized therapy design. Combination of genome-based medicine and individualized model-based drug screening may fulfill the promise of precision medicine for pancreatic cancer. © Springer Science+Business Media, LLC, part of Springer Nature 2018

Developmental sensory experience balances cortical excitation and inhibition

Early in life, neural circuits are highly susceptible to outside influences. The organization of primary auditory cortex (AI) in particular is governed by acoustic experience during the critical period, an epoch near the beginning of postnatal development throughout which cortical synapses and networks are especially plastic1-8. This neonatal sensitivity to the pattern of sensory inputs is believed to be essential for constructing stable and adequately adapted representations of the auditory world and for the acquisition of language skills by children5,9,10. One important principle of synaptic organization in mature brains is the balance between excitation and inhibition, which controls receptive field structure and spatiotemporal flow of neural activity11-15, but it is unknown how and when this excitatory-inhibitory balance is initially established and calibrated. Here we used whole-cell recording to determine the processes underlying the development of synaptic receptive fields in rat AI. We found that, immediately after hearing onset, sensory-evoked excitatory and inhibitory responses were equally strong, although inhibition was less stimulus-selective and mismatched with excitation. However, during the third week of postnatal development, excitation and inhibition became highly correlated. Patterned sensory stimulation drove coordinated synaptic changes across receptive fields, rapidly improved excitatory-inhibitory coupling, and prevented further exposure-induced modifications. Thus the pace of cortical synaptic receptive field development is set by progressive, experience-dependent refinement of intracortical inhibition