Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium-pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

Music Proficiency and Quantification of Absolute Pitch: A Large-Scale Study among Brazilian Musicians.

Absolute pitch (AP) is the ability to identify and name the pitch of a sound without external reference. Often, accuracy and speed at naming isolated musical pitches are correlated with demographic, biological, and acoustical parameters to gain insight into the genesis and evolution of this ability in specific cohorts. However, the majority of those studies were conducted in North America, Europe, or Asia. To fill this gap, here we investigated the pitch-naming performance in a large population of Brazilian conservatory musicians (N = 200). As previously shown, we found that the population performance was rather a continuum than an "all-or-none" ability. By comparing the observed distribution of correct responses to a theoretical binomial distribution, we estimated the prevalence of AP as being 18% amongst regular music students. High accuracy thresholds (e.g., 85% of correct responses) yielded a prevalence of 4%, suggesting that AP might have been underestimated in previous reports. Irrespective of the threshold used, AP prevalence was higher in musicians who started their musical practice and formal musical education early in life. Finally, we compared the performance of those music students (average proficiency group) with another group of students selected to take part in the conservatory orchestra (high proficiency group, N = 30). Interestingly, the prevalence of AP was higher in the latter in comparison to the former group. In addition, even when the response was incorrect, the mean absolute deviation from the correct response was smaller in the high proficiency group compared to the average proficiency group (Glass's Δ: 0.5). Taken together, our results show that the prevalence of AP in Brazilian students is similar to other non-tonal language populations, although this measure is highly dependent on the scoring threshold used. Despite corroborating that early involvement with musical practice and formal education can foster AP ability, the present data suggest that music proficiency may also play an important role in AP expression.

Vesicular acetylcholine transporter knock-down mice are more susceptible to pilocarpine induced status epilepticus.

The pilocarpine (PILO) animal model of Temporal Lobe Epilepsy (TLE) portrays the most common changes in hippocampal circuitry found in human TLE. The acute cholinergic insult induces status epilepticus (SE), which triggers an overwhelming set of plastic events that result on late spontaneous recurrent limbic seizures. It has been suggested that the cholinergic system plays an important role in the synchronization required for ictogenesis. We took advantage of a knock-down animal model for the vesicular acetylcholine transporter (VAChT KD) to investigate seizure genesis in a model of cholinergic dysfunction. We induced SE in VAChT KD and wild-type (WT) mice by a single intraperitoneal injection of PILO in order to evaluate susceptibility to seizures. Video-EEG recordings evaluated epileptiform activity and ictal behavior onset. The hypothesis tested is that innate cholinergic hypofunction could result in increased susceptibility to PILO. VAChT KD(HOM) mice showed shorter latency for the first epileptiform discharge and for the first seizure episode, when compared to other groups. The duration of these seizure episodes, however, were not statistically different among experimental groups. On the other hand, VAChT KD(HOM) had the shortest latency to isoelectric EEG, when compared to WT and KD(HET). Our results indicate that a reduction of brain VAChT protein to the levels found in VAChT KD(HOM) mice alters the epileptic response to PILO. Thus, fine-tuning modulation of cholinergic tone can affect the susceptibility of epileptic responses to pilocarpine.

Synaptic plasticity of the CA3 commissural projection in epileptic rats: an in vivo electrophysiological study.

The hippocampal commissural system has recently been found to participate in the generation of mirror foci after kainate-induced epileptiform discharges. In the present study we have evaluated the electrophysiological alterations in the ventral commissural hippocampal system that originates in the pyramidal CA3 cells and connects to the contralateral CA3 pyramidal cells. The recordings were performed in epileptic rats 24 h after an early behavioural spontaneous seizure between 5 and 21 days after pilocarpine-induced status epilepticus. Epileptic animals presented a marked increase in neuronal excitability after contralateral CA3 stimulation, characterized by a shift to the left in the input-output curve and the clear appearance of a population spike. Input-output curves showed that maximum population excitatory postsynaptic potential (pEPSP) amplitude was decreased by 30%, which could be related to cell death in these regions. Using paired-pulse protocols to evaluate a fast form of synaptic plasticity (i.e. paired-pulse facilitation) we observed that, despite the similar pEPSP amplitude between control and experimental groups, only epileptic animals showed strong paired-pulse population spike facilitation up to 500 ms interstimulus intervals. Despite increased excitability and pyramidal cell death, epileptic animals presented a more robust potentiation after high-frequency stimulation than controls, a protocol used to evaluate a slow form of synaptic plasticity (i.e. long-term potentiation). The increased excitability in CA3 pyramidal neurons enhanced the probability of burst activity in these neurons; this could lead to greater CA1 synchronization. The present results might have relevance for the understanding of epileptogenesis and of learning and memory deficits seen in temporal lobe epilepsy.