Development of Parallel Auditory Thalamocortical Pathways for Two Different Behaviors

Auditory thalamocortical connections are organized as parallel pathways that originate in different divisions of the medial geniculate body (MGB). These pathways may be involved in different functions. Surprisingly little is known about the development of these connections. Here we review studies of the organization and development of auditory thalamocortical pathways in the pallid bat. The pallid bat depends primarily on passive hearing of prey-generated noise for localizing prey, while reserving echolocation for general orientation and obstacle avoidance. In the inferior colliculus (IC) and the auditory cortex, physiological studies show that noise and echolocation calls are processed in segregated regions. Injection of retrograde tracers in physiologically characterized cortical sites show that the ventral division of the MGB (MGBv) projects to the cortical region selective for noise. The cortical region selective for echolocation calls receives input from the suprageniculate (SG) nucleus in the dorsal MGB, but not from the MGBv. Taken together, these studies reveal parallel IC–MGB–cortex pathways involved in echolocation and passive listening. There is overlap of thalamocortical pathways during development. At 2-weeks postnatal, when the bat begins to exhibit adult-like hearing thresholds, the SG projects to both noise- and echolocation call-selective regions. The MGBv, as in adults, projects only to the noise-selective region. The connections become adult-like only after 2-months postnatal. These data suggest that parallel auditory thalamocortical pathways may segregate in an experience-dependent fashion, a hypothesis that remains to be tested in any species

The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders

Perineuronal nets (PNN) are extracellular matrix (ECM) assemblies that preferentially ensheath parvalbumin (PV) expressing interneurons. Converging evidence indicates that PV cells and PNN are impaired in a variety of neurological disorders. PNN development and maintenance is necessary for a number of processes within the CNS, including regulation of GABAergic cell function, protection of neurons from oxidative stress, and closure of developmental critical period plasticity windows. Understanding PNN functions may be essential for characterizing the mechanisms of altered cortical excitability observed in neurodegenerative and neurodevelopmental disorders. Indeed, PNN abnormalities have been observed in post-mortem brain tissues of patients with schizophrenia and Alzheimer’s disease. There is impaired development of PNNs and enhanced activity of its key regulator matrix metalloproteinase-9 (MMP-9) in Fragile X Syndrome, a common genetic cause of autism. MMP-9, a protease that cleaves ECM, is differentially regulated in a number of these disorders. Despite this, few studies have addressed the interactions between PNN expression, MMP-9 activity and neuronal excitability. In this review, we highlight the current evidence for PNN abnormalities in CNS disorders associated with altered network function and MMP-9 levels, emphasizing the need for future work targeting PNNs in pathophysiology and therapeutic treatment of neurological disorders

Reusable Multielectrode Array Technique for Electroencephalography in Awake Freely Moving Mice

Translational comparison of rodent models of neurological and neuropsychiatric diseases to human electroencephalography (EEG) biomarkers in these conditions will require multisite rodent EEG on the skull surface, rather than local area electrocorticography (ECoG) or multisite local field potential (LFP) recording. We have developed a technique for planar multielectrode array (MEA) implantation on the mouse skull surface, which enables multisite EEG in awake and freely moving mice and reusability of the MEA probes. With this method, we reliably obtain 30-channel low-noise EEG from awake mice. Baseline and stimulus-evoked EEG recordings can be readily obtained and analyzed. For example, we have demonstrated EEG responses to auditory stimuli. Broadband noise elicits reliable 30-channel auditory event-related potentials (ERPs), and chirp stimuli induce phase-locked EEG responses just as in human sound presentation paradigms. This method is unique in achieving chronic implantation of novel MEA technology onto the mouse skull surface for chronic multisite EEG recordings. Furthermore, we demonstrate a reliable method for reusing MEA probes for multiple serial implantations without loss of EEG quality. This skull surface MEA methodology can be used to obtain simultaneous multisite EEG recordings and to test EEG biomarkers in diverse mouse models of human neurological and neuropsychiatric diseases. Reusability of the MEA probes makes it more cost-effective to deploy this system for various studies

Effects of sound intensity on temporal properties of inhibition in the pallid bat auditory cortex

Auditory neurons in bats that use frequency modulated (FM) sweeps for echolocation are selective for the behaviorally-relevant rates and direction of frequency change. Such selectivity arises through spectrotemporal interactions between excitatory and inhibitory components of the receptive field. In the pallid bat auditory system, the relationship between FM sweep direction/rate selectivity and spectral and temporal properties of sideband inhibition have been characterized. Of note is the temporal asymmetry in sideband inhibition, with low-frequency inhibition (LFI) exhibiting faster arrival times compared to high-frequency inhibition (HFI). Using the two-tone inhibition over time stimulus paradigm, this study investigated the interactions between two sound parameters in shaping sideband inhibition: intensity and time. Specifically, the impact of changing relative intensities of the excitatory and inhibitory tones on arrival time of inhibition was studied. Using this stimulation paradigm, single unit data from the auditory cortex of pentobarbital-anesthetized cortex show that the threshold for LFI is on average ~8 dB lower than HFI. For equal intensity tones near threshold, LFI is stronger than HFI. When the inhibitory tone intensity is increased further from threshold, the strength asymmetry decreased. The temporal asymmetry in LFI versus HFI arrival time is strongest when the excitatory and inhibitory tones are of equal intensities or if excitatory tone is louder. As inhibitory tone intensity is increased, temporal asymmetry decreased suggesting that the relative magnitude of excitatory and inhibitory inputs shape arrival time of inhibition and FM sweep rate and direction selectivity. Given that most FM bats use downward sweeps as echolocation calls, a similar asymmetry in threshold and strength of LFI versus HFI may be a general adaptation to enhance direction selectivity while maintaining sweep-rate selective responses to downward sweeps

Neural Mechanisms of Stimulus Velocity Tuning in the Superior Colliculus

In 1607 Henry IV also began the first monumental plague hospital in Europe, the Hôpital St Louis, designed by Claude Vellefaux (1559-1619). Buildings constructed under Henry IV were typically of brick and stone and drew on the stylistic vocabulary of French architecture of the last third of the 16th century. While the architectural forms of his reign were conservative, his programme was innovative in its social goals and methods of development.; In 1607 Henry IV also began the first monumental plague hospital in Europe, the Hôpital St Louis, designed by Claude Vellefaux (1559-1619). Buildings constructed under Henry IV were typically of brick and stone and drew on the stylistic vocabulary of French architecture of the last third of the 16th century. While the architectural forms of his reign were conservative, his programme was innovative in its social goals and methods of development. Source: Grove Art Online; http://www.oxfordartonline.com/ (accessed 12/15/2008

GABA Shapes a Systematic Map of Binaural Sensitivity in the Auditory Cortex

A consistent organizational feature of auditory cortex is a clustered representation of binaural properties. Here we address two questions. What is the intrinsic organization of binaural clusters and to what extent does intracortical processing contribute to binaural representation. We address these issues in the auditory cortex of the pallid bat. The pallid bat listens to prey-generated noise transients to localize and hunt terrestrial prey. As in other species studied, binaural clusters are present in the auditory cortex of the pallid bat. One cluster contains neurons that require binaural stimulation to be maximally excited, and are commonly termed predominantly binaural (PB) neurons. These neurons do not respond to monaural stimulation of either ear but show a peaked sensitivity to interaural intensity differences (IID) centered near 0 dB IID. We show that the peak IID varies systematically within this cluster. The peak IID is also correlated with the best frequency (BF) of neurons within this cluster. In addition, the IID selectivity of PB neurons is shaped by intracortical GABAergic input. Iontophoresis of GABAA receptor antagonists on PB neurons converts a majority of them to binaurally inhibited (EI) neurons that respond best to sounds favoring the contralateral ear. These data indicate that the cortex does not simply inherit binaural properties from lower levels but instead sharpens them locally through intracortical inhibition. The IID selectivity of the PB cluster indicates that the pallid bat cortex contains an increased representation of the frontal space that may underlie increased localization accuracy in this region