LFP publications

Increased acoustic startle responses (ASR), which represent reduced uncomfortable loudness level in humans, have been reported in middle-aged C57BL/6J mice with sensorineural hearing loss. Although neural plasticity changes in the central auditory system after the peripheral lesions were suggested to underlie this phenomenon, the neurological cause of exaggerated ASR is still not clear. In this study, the local field potentials and firing rates of the caudal pontine reticular nucleus (PnC), which plays a major role in the ASR pathway, were recorded in 2-month- and 6-month-old C57BL/6 J mice. Consistent with our previous studies, the amplitude of ASR increased, and the threshold of ASR decreased in the 6-month-old mice after developing 20–40 dB hearing loss. The PnC response induced by high-frequency stimuli (>20 kHz) decreased in the 6-month group, whereas the PnC response induced by low-frequency stimuli (<12 kHz) showed a significant increase in the 6-month group compared to the 2-month group. The enhancement of PnC response is similar to the ASR increase found in the 6-month-old C57 mice. Our results suggest that the high-frequency hearing loss caused an increase in PnC sensitivity in the C57 mice which may enhance ASRs.

The sensitivity of ocular dominance to regulation by monocular deprivation is the canonical model of plasticity confined to a critical period. However, we have previously shown that visual deprivation through dark exposure (DE) reactivates critical period plasticity in adults. Previous work assumed that the elimination of visual input was sufficient to enhance plasticity in the adult mouse visual cortex. In contrast, here we show that light reintroduction (LRx) after DE is responsible for the reactivation of plasticity. LRx triggers degradation of the ECM, which is blocked by pharmacological inhibition or genetic ablation of matrix metalloproteinase-9 (MMP-9). LRx induces an increase in MMP-9 activity that is perisynaptic and enriched at thalamo-cortical synapses. The reactivation of plasticity by LRx is absent in Mmp9−/− mice, and is rescued by hyaluronidase, an enzyme that degrades core ECM components. Thus, the LRx-induced increase in MMP-9 removes constraints on structural and functional plasticity in the mature cortex.

Successful speech perception in real-world environments requires that the auditory system segregate competing voices that overlap in frequency and time into separate streams. Vowels are major constituents of speech and are comprised of frequencies (harmonics) that are integer multiples of a common fundamental frequency (F0). The pitch and identity of a vowel are determined by its F0 and spectral envelope (formant structure), respectively. When two spectrally overlapping vowels differing in F0 are presented concurrently, they can be readily perceived as two separate “auditory objects” with pitches at their respective F0s. A difference in pitch between two simultaneous vowels provides a powerful cue for their segregation, which in turn, facilitates their individual identification. The neural mechanisms underlying the segregation of concurrent vowels based on pitch differences are poorly understood. Here, we examine neural population responses in macaque primary auditory cortex (A1) to single and double concurrent vowels (/a/ and /i/) that differ in F0 such that they are heard as two separate auditory objects with distinct pitches. We find that neural population responses in A1 can resolve, via a rate-place code, lower harmonics of both single and double concurrent vowels. Furthermore, we show that the formant structures, and hence the identities, of single vowels can be reliably recovered from the neural representation of double concurrent vowels. We conclude that A1 contains sufficient spectral information to enable concurrent vowel segregation and identification by downstream cortical areas.

The rhizome of Gastrodia elata (GE), a herb medicine, has been used for treatment of neuronal disorders in Eastern Asia for hundreds of years. Parishin C is a major ingredient of GE. In this study, the i.c.v. injection of soluble Aβ 1-42 oligomers model of LTP injury was used. We investigated the effects of parishin C on the improvement of LTP in soluble Aβ 1-42 oligomer-injected rats and the underlying electrophysiological mechanisms. Parishin C (i.p. or i.c.v.) significantly ameliorated LTP impairment induced by i.c.v. injection of soluble Aβ 1-42 oligomers. In cultured hippocampal neurons, soluble Aβ 1-42 oligomers significantly inhibited NMDAR currents while not affecting AMPAR currents and voltage-dependent currents. Pretreatment with parishin C protected NMDA receptor currents from the damage induced by Aβ. In summary, parishin C improved LTP deficits induced by soluble Aβ 1-42 oligomers. The protection by parishin C against Aβ-induced LTP damage might be related to NMDA receptors.

Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ)-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes.

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus.

Background The basal forebrain (BF) regulates cortical activity by the action of cholinergic projections to the cortex. At the same time, it also sends substantial GABAergic projections to both cortex and thalamus, whose functional role has received far less attention. We used deep brain stimulation (DBS) in the BF, which is thought to activate both types of projections, to investigate the impact of BF activation on V1 neural activity. Results BF stimulation robustly increased V1 single and multi-unit activity, led to moderate decreases in orientation selectivity and a remarkable increase in contrast sensitivity as demonstrated by a reduced semi-saturation contrast. The spontaneous V1 local field potential often exhibited spectral peaks centered at 40 and 70 Hz as well as reliably showed a broad γ-band (30-90 Hz) increase following BF stimulation, whereas effects in a low frequency band (1-10 Hz) were less consistent. The broad γ-band, rather than low frequency activity or spectral peaks was the best predictor of both the firing rate increase and contrast sensitivity increase of V1 unit activity. Conclusions We conclude that BF activation has a strong influence on contrast sensitivity in V1. We suggest that, in addition to cholinergic modulation, the BF GABAergic projections play a crucial role in the impact of BF DBS on cortical activity.

It is not known how visual cortical neurons react to several moving objects and how their firing to the motion of one object is affected by neurons firing to another moving object. Here we combine imaging of voltage sensitive dye (VSD) signals, reflecting the population membrane potential from ferret visual areas 17, 18, 19, and 21, with laminar recordings of multiunit activity, (MUA), when two bars moved toward each other in the visual field, occluded one another, and continued on in opposite directions. Two zones of peak MUA, mapping the bars' motion, moved toward each other along the area 17/18 border, which in the ferret maps the vertical meridian of the field of view. This was reflected also in the VSD signal, at both the 17/18 border as well as at the 19/21 border with a short delay. After some 125 ms at the area 19/21 border, the VSD signal increased and became elongated in the direction of motion in front of both of the moving representations. This was directly followed by the phase of the signal reversing and travelling back from the 19/21 border toward the 17/18 border, seemingly without respect for retinotopic boundaries, where it arrived at 150 ms after stimulus onset. At this point the VSD signal in front of the moving bar representations along the 17/18 border also increased and became elongated in the direction of object motion; the signal now being the linear sum of what has been observed in response to single moving bars. When the neuronal populations representing the bars were some 600 μm apart on the cortex, the dye signal and laminar MUA decreased strongly, with the MUA scaling to that of a single bar during occlusion. Despite a short rebound of the dye signal and MUA, the MUA after the occlusion was significantly depressed. The interactions between the neuronal populations mapping the bars' position, and the neurons in between these populations were, apart from 19/21 to 17/18 interaction, mainly lateral-horizontal; first excitatory and inducing firing at the site of future occlusion, then inhibitory just prior to occlusion. After occlusion the neurons that had fired already to the first bar showed delayed and prolonged inhibition in response to the second bar. Thus, the interactions that were particular to the occlusion condition in these experiments were local and inhibitory at short cortical range, and delayed and inhibitory after the occlusion when the bars moved further apart.

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.

Adaptive behavior depends on an animal's ability to ignore uninformative stimuli, such as repeated presentations of the same stimulus, and, instead, detect informative, novel stimuli in its environment. The primate prefrontal cortex (PFC) is known to play a central role in this ability. However, the neural mechanisms underlying the ability to differentiate between repeated and novel stimuli are not clear. We hypothesized that the coupling between different frequency bands of the local field potential (LFP) underlies the PFC's role in differentiating between repeated and novel stimuli. Specifically, we hypothesized that whereas the presentation of a novel-stimulus induces strong cross-frequency coupling, repeated presentations of the same stimulus attenuates this coupling. To test this hypothesis, we recorded LFPs from the ventrolateral PFC (vPFC) of rhesus monkeys while they listened to a novel vocalization and repeated presentations of the same vocalization. We found that the cross-frequency coupling between the gamma-band amplitude and theta-band phase of the LFP was modulated by repeated presentations of a stimulus. During the first (novel) presentation of a stimulus, gamma-band activity was modulated by the theta-band phase. However, with repeated presentations of the same stimulus, this cross-frequency coupling was attenuated. These results suggest that cross-frequency coupling may play a role in the neural computations that underlie the differentiation between novel and repeated stimuli in the vPFC.

When an object is introduced moving in the visual field of view, the object maps with different delays in each of the six cortical layers in many visual areas by mechanisms that are poorly understood. We combined voltage sensitive dye (VSD) recordings with laminar recordings of action potentials in visual areas 17, 18, 19 and 21 in ferrets exposed to stationary and moving bars. At the area 17/18 border a moving bar first elicited an ON response in layer 4 and then ON responses in supragranular and infragranular layers, identical to a stationary bar. Shortly after, the moving bar mapped as moving synchronous peak firing across layers. Complex dynamics evolved including feedback from areas 19/21, the computation of a spatially restricted pre-depolarization (SRP), and firing in the direction of cortical motion prior to the mapping of the bar. After 350 ms, the representations of the bar (peak firing and peak VSD signal) in areas 19/21 and 17/18 moved over the cortex in phase. The dynamics comprise putative mechanisms for automatic saliency of novel moving objects, coherent mapping of moving objects across layers and areas, and planning of catch-up saccades.