laser-scanning-photostimulation-optogenetically-targeted-forebrain

Laser-scanning Photostimulation of Optogenetically Targeted Forebrain Circuits

The sensory forebrain is composed of intricately connected cell types, of which functional properties have yet to be fully elucidated. Understanding the ...

Louisiana State University

Two tonotopic areas, the primary auditory cortex (AI) and the anterior auditory field (AAF), are the primary cortical fields in the cat auditory system. They receive largely independent, concurrent thalamocortical projections from the different thalamic divisions despite their hierarchical equivalency. The parallel streams of thalamic inputs to AAF and AI suggest that AAF neurons may differ from AI neurons in physiological properties. Although a modular functional organization in cat AI has been well documented, little is known about the internal organization of AAF beyond tonotopy. We studied how basic receptive field parameters (RFPs) are spatially organized in AAF with single- and multiunit recording techniques. A distorted tonotopicity with an underrepresentation in midfrequencies (1 and 5 kHz) and an overrepresentation in the high-frequency range was found. Spectral bandwidth (Q-values) and response threshold were significantly correlated with characteristic frequency (CF). To understand whether AAF has a modular organization of RFPs, CF dependencies were eliminated by a nonparametric, local regression model, and the residuals (difference between the model and observed values) were evaluated. In a given isofrequency domain, clusters of low or high residual RFP values were interleaved for threshold, spectral bandwidth, and latency, suggesting a modular organization. However, RFP modules in AAF were not expressed as robustly as in AI. A comparison of RFPs between AAF and AI shows that AAF neurons were more broadly tuned and had shorter latencies than AI neurons. These physiological field differences are consistent with anatomical evidence of largely independent, concurrent thalamocortical projections in AI and AAF, which strongly suggest field-specific processing.

Modular functional organization of cat anterior auditory field.

The basis for multiple representations of equivalent frequency ranges in auditory cortex was studied with physiological and anatomical methods. Our goal was to trace the convergence of thalamic, commissural, and corticocortical information upon two tonotopic fields in the cat, the primary auditory cortex (AI) and the anterior auditory field (AAF). Both fields are among the first cortical levels of processing. After neurophysiological mapping of characteristic frequency, we injected different retrograde tracers at separate, frequency-matched loci in AI and AAF. We found differences in their projections that support the notion of largely segregated parallel processing streams in the auditory thalamus and cerebral cortex. In each field, ipsilateral cortical input amounts to approximately 70% of the number of cells projecting to an isofrequency domain, while commissural and thalamic sources are each approximately 15%. Labeled thalamic and cortical neurons were concentrated in tonotopically predicted regions and in smaller loci far from their spectrally predicted positions. The few double-labeled thalamic neurons (<2%) are consistent with the hypothesis that information to AI and AAF travels along independent processing streams despite widespread regional overlap of thalamic input sources. Double labeling is also sparse in both the corticocortical and commissural systems ( approximately 1%), confirming their independence. The segregation of frequency-specific channels within thalamic and cortical systems is consistent with a model of parallel processing in auditory cortex. The global convergence of cells outside the targeted frequency domain in AI and AAF could contribute to context-dependent processing and to intracortical plasticity and reorganization.

Concurrent tonotopic processing streams in auditory cortex.

We describe the central projections of physiologically characterized auditory receptor neurons of crickets as revealed by confocal microscopy. Receptors tuned to ultrasonic frequencies (similar to those produced by echolocating, insectivorous bats), to a mid-range of frequencies, and a subset of those tuned to low, cricket-like frequencies have similar projections, terminating medially within the auditory neuropile. Quantitative analysis shows that despite the general similarity of these projections they are tonotopic, with receptors tuned to lower frequencies terminating more medially. Another subset of cricket-song-tuned receptors projects more laterally and posteriorly than the other types. Double-fills of receptors and identified interneurons show that the three medially projecting receptor types are anatomically well positioned to provide monosynaptic input to interneurons that relay auditory information to the brain and to interneurons that modify this ascending information. The more laterally and posteriorly branching receptor type may not interact directly with this ascending pathway, but is well positioned to provide direct input to an interneuron that carries auditory information to more posterior ganglia. These results suggest that information about cricket song is segregated into functionally different pathways as early as the level of receptor neurons. Ultrasound-tuned and mid-frequency tuned receptors have approximately twice as many varicosities, which are sites of transmitter release, per receptor as either anatomical type of cricket-song-tuned receptor. This may compensate in part for the numerical under-representation of these receptor types.

Central projections of auditory receptor neurons of crickets.

The mechanisms by which hearing selectivity is elaborated and refined in early development are very incompletely determined. In this study, we documented contributions of progressively maturing inhibitory influences on the refinement of spectral and temporal response properties in the primary auditory cortex. Inhibitory receptive fields (IRFs) of infant rat auditory cortical neurons were spectrally far broader and had extended over far longer duration than did those of adults. The selective refinement of IRFs was delayed relative to that of excitatory receptive fields by an approximately 2-week period that corresponded to the critical period for plasticity. Local application of a GABA(A) receptor antagonist revealed that intracortical inhibition contributes to this progressive receptive field maturation for response selectivity in frequency. Conversely, it had no effect on the duration of IRFs or successive-signal cortical response recovery times. The importance of exposure to patterned acoustic inputs was suggested when both spectral and temporal IRF maturation were disrupted in rat pups reared in continuous, moderate-intensity noise. They were subsequently renormalized when animals were returned to standard housing conditions as adults.

Development of spectral and temporal response selectivity in the auditory cortex.

Primary sensory cortical areas are characterized by orderly and largely independent representations of several receptive field properties. This is expressed in multiple, spatially overlaying parameter distributions, such as orientation preference, spatial frequency, and ocular dominance maps in the primary visual cortex. In the auditory cortex, two main and presumably independent representational parameters are the center frequency and the frequency extent of spectral tuning curves. Here we demonstrate interactions between cortical tonotopic gradient and spectral bandwidth modules in cat primary auditory cortex (AI). First, the spatial representation of spectral integration is not equally expressed across the whole frequency range in AI. Narrow-bandwidth modules are found only in the mid-frequency region (5-20 kHz). Thus spectral integration properties delineate three frequency regions (<5, 5-20, and >20 kHz) in cat AI. Second, the extent of spectral integration covaries with the local tonotopic gradient in the low- and mid-frequency ranges. Regions with a shallow frequency gradient tend to have narrower spectral integration than those with a steep gradient. These relationships between spectral selectivity and frequency gradient constrain forebrain models of thalamo- and corticocortical convergence and connectivity and may reflect the processing of behaviorally relevant stimulus constellations.

Spatial interaction between spectral integration and frequency gradient in primary auditory cortex.

A central goal in auditory neuroscience is to understand the neural coding of species-specific communication and human speech sounds. Low-rate repetitive sounds are elemental features of communication sounds, and core auditory cortical regions have been implicated in processing these information-bearing elements. Repetitive sounds could be encoded by at least three neural response properties: 1) the event-locked spike-timing precision, 2) the mean firing rate, and 3) the interspike interval (ISI). To determine how well these response aspects capture information about the repetition rate stimulus, we measured local group responses of cortical neurons in cat anterior auditory field (AAF) to click trains and calculated their mutual information based on these different codes. ISIs of the multiunit responses carried substantially higher information about low repetition rates than either spike-timing precision or firing rate. Combining firing rate and ISI codes was synergistic and captured modestly more repetition information. Spatial distribution analyses showed distinct local clustering properties for each encoding scheme for repetition information indicative of a place code. Diversity in local processing emphasis and distribution of different repetition rate codes across AAF may give rise to concurrent feed-forward processing streams that contribute differently to higher-order sound analysis.

Encoding of temporal information by timing, rate, and place in cat auditory cortex.

Auditory cortex updates incoming information on a segment by segment basis for human speech and animal communication. Measuring repetition rate transfer functions (RRTFs) captures temporal responses to repetitive sounds. In this study, we used repetitive click trains to describe the spatial distribution of RRTF responses in cat anterior auditory field (AAF) and to discern potential variations in local temporal processing capacity. A majority of RRTF filters are band-pass. Temporal parameters estimated from RRTFs and corrected for characteristic frequency or latency dependencies are non-homogeneously distributed across AAF. Unlike the shallow global gradient observed in spectral receptive field parameters, transitions from loci with high to low temporal parameters are steep. Quantitative spatial analysis suggests non-uniform, circumscribed local organization for temporal pattern processing superimposed on global organization for spectral processing in cat AAF.

Spatial organization of repetition rate processing in cat anterior auditory field.

Studies of patterned spontaneous activity can elucidate how the organization of neural circuits emerges. Using in vivo two-photon Ca(2+) imaging, we studied spatio-temporal patterns of spontaneous activity in the optic tectum of Xenopus tadpoles. We found rhythmic patterns of global synchronous spontaneous activity between neurons, which depends on visual experience and developmental stage. By contrast, synchronous spontaneous activity between non-neuronal cells is mediated more locally. To understand the source of the neuronal spontaneous activity, input to the tectum was systematically removed. Whereas removing input from the visual or mechanosensory system alone had little effect on patterned spontaneous activity, removing input from both systems drastically altered it. These results suggest that either input is sufficient to maintain the intrinsically generated spontaneous activity and that patterned spontaneous activity results from input from multisensory systems. Thus, the amphibian midbrain differs from the mammalian visual system, whose spontaneous activity is controlled by retinal waves.

Article	Year
Modular functional organization of cat anterior auditory field. Journal of neurophysiology\| PubMed ID: 15014102	2004
Concurrent tonotopic processing streams in auditory cortex. Cerebral cortex (New York, N.Y. : 1991)\| PubMed ID: 15028648	2004
Central projections of auditory receptor neurons of crickets. The Journal of comparative neurology\| PubMed ID: 16261528	2005
Development of spectral and temporal response selectivity in the auditory cortex. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 16263924	2005
Spatial interaction between spectral integration and frequency gradient in primary auditory cortex. Journal of neurophysiology\| PubMed ID: 17855587	2007
Encoding of temporal information by timing, rate, and place in cat auditory cortex. PloS one\| PubMed ID: 20657832	2010
Spatial organization of repetition rate processing in cat anterior auditory field. Hearing research\| PubMed ID: 21569829	2011
Global hyper-synchronous spontaneous activity in the developing optic tectum. Scientific reports\| PubMed ID: 23531884	2013

Kazuo Imaizumi

Biography

JoVE Journal Publications

Other Publications