Neuronal identification of acoustic signal periodicity

Acoustic signals transmit information by temporal characteristics and envelope periodicity as well as by their frequency content. Many animals can extract the frequency content of a signal by means of specialized organs such as the cochlea but for the detection and identification of higher-order periodicity, e.g., amplitude modulations, this type of organ is useless. In addition, many animals do not have a cochlea but still depend on a reliable identification of different frequencies in the vast variety of acoustic signals they perceive in their natural environment. Hence, neural mechanisms to decode periodicity information must exist. We present a detailed mathematical analysis of a recurrent and a feedforward model of neuronal periodicity extraction and discuss basic constraints for neuronal circuitry performing such a task in a biological system. Both the recurrent and the feedforward model perform well using neuronal parameters typical for the auditory system. Performance is limited mainly by the temporal precision of the connections between the neurons.     

Behavioral sterility of hybrid males in acoustically communicating grasshoppers (Acrididae,Gomphocerinae)

The effectiveness of hybridization barriers determines whether two species remain reproductively isolated when their populations come into contact. We investigated acoustic mating signals and associated leg movements responsible for song creation of hybrids between the grasshopper species Chorthippus biguttulus and C. brunneus to study whether and how songs of male hybrids contribute to reproductive isolation between these sympatrically occurring species. Songs of F1, F2, and backcross hybrids were intermediate between those of both parental species in terms phrase number and duration. In contrast, species-specific syllable structure within phrases was largely lost in hybrids and was produced, if at all, in an irregular and imperfect manner. These divergences in inheritance of different song parameters are likely the result of incompatibility of neuronal networks that control stridulatory leg movements in hybrids. It is highly probable that songs of hybrid males are unattractive to females of either parental species because they are intermediate in terms of phrase duration and lack a clear syllable structure. Males of various hybrid types (F1, F2, and backcrosses) are behaviorally sterile because their songs fail to attract mates.     

Enhancement of Sodium Current in NG108-15 Cells during Neural Differentiation is Mainly due to an Increase in NaV1.7 Expression

It is well known that morphological and functional changes during neural differentiation sometimes accompany the expression of various voltage-gated ion channels. In this work, we investigated whether the enhancement of sodium current in differentiated neuroblastoma × glioma NG108-15 cells treated with dibutyryl cAMP is related to the expression of voltage-gated sodium channels. The results were as follows. (1) Sodium current density on peak voltage in differentiated cells was significantly enhanced compared with that in undifferentiated cells, as detected by the whole-cell patch clamp method. The steady-state inactivation curve in differentiated cells was similar to that for undifferentiated cells, but a hyperpolarized shift in the activation curve for differentiated cells was observed. The sodium currents of differentiated and undifferentiated cells were completely inhibited by 10⁻⁷ M tetrodotoxin (TTX). (2) The only Na_V mRNA with an increased expression level during neuronal differentiation was that for Na_V1.7, as observed by real-time PCR analysis. (3) The increase in the level of Na_V1.7 α subunit expression during neuronal differentiation was also observed by immunocytochemistry; in particular, the localization of Na_V1.7 α subunits on the soma, varicosities and growth cone was significant. These results suggest that the enhancement of TTX-sensitive sodium current density in differentiated NG108-15 cells is mainly due to the increase in the expression of the TTX-sensitive voltage-gated Na⁺ channel, Na_V1.7.     

Direct Evidence for Calpain Involvement in Apoptotic Death of Neurons in Spinal Cord Injury in Rats and Neuroprotection with Calpain Inhibitor

To demonstrate calpain involvement in neurodegeneration in rat spinal cord injury (SCI), we examined SCI segments for DNA fragmentation, neurons for calpain overexpression, neuronal death, and neuroprotection with calpain inhibitor (E-64-d). After the induction of SCI (40 g cm force) on T12, rats were treated within 15 min with vehicle (DMSO) or E-64-d. Sham animals underwent laminectomy only. Animals were sacrificed at 24 h, and five 1-cm long spinal cord segments were collected: two rostral (S1 and S2), one lesion (S3), and two caudal segments (S4 and S5). Agarose gel electrophoresis of DNA samples isolated from the SCI segments showed both random and internucleosomal DNA fragmentation indicating occurrence of necrosis as well as apoptosis mostly in the lesion, moderately in caudal, and slightly in rostral segments from SCI rats. Treatment of SCI rats with E-64-d (1 mg/kg) reduced DNA fragmentation in all segments. The lesion and adjacent caudal segments (S3 and S4) were further investigated by in situ double-immunofluorescent labelings that showed increase in calpain expression in neurons in SCI rats and decrease in calpain expression in SCI rats treated with E-64-d. In situ combined TUNEL and double-immunofluorescent labelings directly detected co-localization of neuronal death and calpain overexpressin in SCI rats treated with only vehicle while attenuation of neuronal death in SCI rats treated with E-64-d. Previous studies from our laboratory indirectly showed neuroprotective effect of E-64-d in SCI rats. Our current results provide direct in situ evidence for calpain involvement in neuronal death and neuroprotective efficacy of E-64-d in lesion and penumbra in SCI rats. Special issue in honor of Naren Banik.     

Indices of Metabolic Dysfunction and Oxidative Stress

Metabolic alterations are a key player involved in the onset of Alzheimer disease pathophysiology and, in this review, we focus on diet, metabolic rate, and neuronal size differences that have all been shown to play etiological and pathological roles in Alzheimer disease. Specifically, one of the earliest manifestations of brain metabolic depression in these patients is a sustained high caloric intake meaning that general diet is an important factor to take in account. Moreover, atrophy in the vasculature and a reduced glucose transporter activity for the vessels is also a common feature in Alzheimer disease. Finally, the overall size of neurons is larger in cases of Alzheimer disease than that of age-matched controls and, in individuals with Alzheimer disease, neuronal size inversely correlates with disease duration and positively associates with oxidative stress. Overall, clarifying cellular and molecular manifestations involved in metabolic alterations may contribute to a better understanding of early Alzheimer disease pathophysiology. Special issue dedicated to John P. Blass. Gemma Casadesus and Paula I. Moreira contributed equally to this paper. Aspects of this paper were previously presented in Neurochemical Research 28, 1549–1552, 2003 and the Journal of Alzheimer’s Disease 1, 203–206, 1999 and were used here with permission.     

Cocaine withdrawal and neuro-adaptations in ion channel function

Chronic exposure to psychostimulants induces neuro-adaptations in ion channel function of dopamine (DA)-innervated cells localized within the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Although neuroplasticity in ion channel function is initially found in drug-sensitized animals, it has recently been believed to underlie the withdrawal effects of cocaine, including craving that leads to relapse in human addicts. Recent studies have also revealed remarkable differences in altered ion channel activities between mPFC pyramidal neurons and medium spiny NAc neurons in cocaine-withdrawn animals. In response to psychostimulant or certain “excitatory” stimuli, increased intrinsic excitability is found in mPFC pyramidal neurons, whereas decreased excitability is observed in medium spiny NAc cells in drug-withdrawn animals compared to drug-free control animals. These changes in ion channel function are modulated by interrupted DA/Ca²⁺ signaling with decreased DA D2 receptor function but increased D1 receptor signaling. More importantly, they are correlated to behavioral changes in cocaine-withdrawn human addicts and sensitized animals. Based on growing evidence, researchers have proposed that cocaine-induced neuro-adaptations in ion channel activity and DA/Ca²⁺ signaling in mPFC pyramidal neurons and medium spiny NAc cells may be the fundamental cellular mechanism underlying the cocaine withdrawal effects observed in human addicts.     

Inhibition of rhythmic spiking by colored noise in neural systems

We study the effect of colored noise on the rhythmic spiking activity of neural systems in this paper. The phenomenon of the so-called inverse stochastic resonance , that is, noise with appropriate intensity suppresses the spiking activity in neural systems, is clearly observed in a special parameter regime. We find that the inhibition effect of colored noise is stronger than that of Gaussian white noise. Furthermore, our simulation results show that the inhibition effect of colored noise provides a useful mechanism for the generation of synchronized burst in type-2 mixed-feed-forward-feedback loop neuronal network motif, which indicates that such inhibition effect might have some biological implications.     

Id4 is required for the correct timing of neural differentiation

Complex intrinsic and extrinsic mechanisms determine neural cell fate during development of the nervous system. Using Id4 deficient mice, we show that Id4 is required for normal development of the central nervous system (CNS), timing neural differentiation in the developing forebrain. In the absence of Id4, the ventricular zone of the neocortex, future hippocampus as well as lateral and medial ganglionic eminences exhibited a 20-30% reduction in mitotic neural precursor cells (NPCs). Although the number of apoptotic cells was significantly increased, the neocortex of Id4(-/-) embryos was consistently thicker due to premature neuronal differentiation, which resulted in an increase in early-born neurons in the adult Id4(-/-) cortex. Late-born cortical neurons and astrocytes in the cortex, septum, hippocampus and caudate putamen of Id4(-/-) adult brains were decreased, however, likely due to the depletion of the NPC pool. Consequently, adult Id4(-/-) brains were smaller and exhibited enlarged ventricles. In vitro analysis of neurosphere cultures revealed that proliferation of Id4-deficient NPCs was impaired and that BMP2-mediated astrocyte differentiation was accelerated in the absence of Id4. Together, these in vivo and in vitro data suggest a crucial role for Id4 in regulating NPC proliferation and differentiation.