Spectral processing deficits in belt auditory cortex following early postnatal lesions of somatosensory cortex.

Induced or genetically based cortical laminar malformations in somatosensory cortex have been associated with perceptual and acoustic processing deficits in mammals. Perinatal freeze-lesions of developing rat primary somatosensory (S1) cortex induce malformations resembling human microgyria. Induced microgyria located in parietal somatosensory cortex have been linked to reduced behavioral detection of rapid sound transitions and altered spectral processing in primary auditory cortex (A1). Here we asked whether belt auditory cortex function would be similarly altered in rats with S1 microgyria (MG+). Pure-tone acoustic response properties were assessed in A1 and ventral auditory (VAF) cortical fields with Fourier optical imaging and multi-unit recordings. Three changes in spectral response properties were observed in both A1 and VAF in MG+ rats: 1) multi-unit response magnitudes were reduced 2) optical and multi-unit frequency responses were more variable; 3) at high sound levels units responded to a broader range of pure-tone frequencies. Optical and multi-unit pure-tone response magnitudes were both reduced for low sound levels in VAF but not A1. Sound level "tuning" was reduced in VAF but not in A1. Finally, in VAF frequency tuning and spike rates near best frequency were both altered for mid- but not high-frequency recording sites. These data suggest that VAF belt auditory cortex is more vulnerable than A1 to early postnatal induction of microgyria in neighboring somatosensory cortex.

Two thalamic pathways to primary auditory cortex.

Neurons in the center of cat primary auditory cortex (AI) respond to a narrow range of sound frequencies and the preferred frequencies in local neuron clusters are closely aligned in this central narrow bandwidth region (cNB). Response preferences to other input parameters, such as sound intensity and binaural interaction, vary within cNB; however, the source of this variability is unknown. Here we examined whether input to the cNB could arise from multiple, anatomically independent subregions in the ventral nucleus of the medial geniculate body (MGBv). Retrograde tracers injected into cNB labeled discontinuous clusters of neurons in the superior (sMGBv) and inferior (iMGBv) halves of the MGBv. Most labeled neurons were in the sMGBv and their density was greater, iMGBv somata were significantly larger. These findings suggest that cNB projection neurons in superior and iMGBv have distinct anatomic and possibly physiologic organization.

Early cortical damage in rat somatosensory cortex alters acoustic feature representation in primary auditory cortex.

Early postnatal freeze-lesions to the cortical plate result in malformations resembling human microgyria. Microgyria in primary somatosensory cortex (S1) of rats are associated with a reduced behavioral detection of rapid auditory transitions and the loss of large cells in the thalamic nucleus projecting to primary auditory cortex (A1). Detection of slow transitions in sound is intact in animals with S1 microgyria, suggesting dissociation between responding to slow versus rapid transitions and a possible dissociation between levels of auditory processing affected. We hypothesized that neuronal responses in primary auditory cortex (A1) would be differentially reduced for rapid sound repetitions but not for slow sound sequences in animals with S1 microgyria. We assessed layer IV cortical responses in primary auditory cortex (A1) to single pure-tones and periodic noise bursts (PNB) in rats with and without S1 microgyria. We found that responses to both types of acoustic stimuli were reduced in magnitude in animals with microgyria. Furthermore, spectral resolution was degraded in animals with microgyria. The cortical selectivity and temporal precision were then measured with conventional methods for PNB and tone-stimuli, but no significant changes were observed between microgyric and control animals. Surprisingly, the observed spike rate reduction was similar for rapid and slow temporal modulations of PNB stimuli. These results suggest that acoustic processing in A1 is indeed altered with early perturbations of neighboring cortex. However, the type of deficit does not affect the temporal dynamics of the cortical output. Instead, acoustic processing is altered via a systematic reduction in the driven spike rate output and spectral integration resolution in A1. This study suggests a novel form of plasticity, whereas early postnatal lesions of one sensory cortex can have a functional impact on processing in neighboring sensory cortex.

Functional convergence of response properties in the auditory thalamocortical system.

One of the brain's fundamental tasks is to construct and transform representations of an animal's environment, yet few studies describe how individual neurons accomplish this. Our results from correlated pairs in the auditory thalamocortical system show that cortical excitatory receptive field regions can be directly inherited from thalamus, constructed from smaller inputs, and assembled by the cooperative activity of neuronal ensembles. The prevalence of functional thalamocortical connectivity is strictly governed by tonotopy, but connection strength is not. Finally, spectral and temporal modulation preferences in cortex may differ dramatically from the thalamic input. Our observations reveal a radical reconstruction of response properties from auditory thalamus to cortex, and illustrate how some properties are propagated with great fidelity while others are significantly transformed or generated intracortically.

Deterministic dynamics emerging from a cortical functional architecture.

Cerebral cortex has a range of interconnected functional architectures. Some appear random and without structure, while others are geometrical. Although the biological details certainly constrain spatial temporal patterns in neural networks, the influence that the laws of deterministic dynamics bring to bear on even isolated simple geometries are unknown. Layer II/III of primary visual cortex has long range horizontal connections with projections to and from other layers. The long range excitatory connections were modeled in isolation as an isolated laterally connected functional architecture. The Hodgkin-Huxley or Pinsky-Rinzel equations were used to simulate the neuronal elements. Waves of activity could propagate through the functional architecture; depending on the synaptic kinetics, the system could settle down into quiescence, oscillations, or seemingly random behavior. Order could be found in random-looking behavior by the application of techniques from chaos theory. Furthermore, the range and transitions of the temporal patterns in the modeled collection of neurons are similar to those found in other non-linear systems. The possibility that the temporal patterns of neurons in situ are also constrained by these mathematical laws is discussed.

Modular organization of intrinsic connections associated with spectral tuning in cat auditory cortex.

Many response properties in primary auditory cortex (AI) are segregated spatially and organized topographically as those in primary visual cortex. Intensive study has not revealed an intrinsic, anatomical organizing principle related to an AI functional topography. We used retrograde anatomic tracing and topographic physiologic mapping of acoustic response properties to reveal long-range (> or = 1.5 mm) convergent intrinsic horizontal connections between AI subregions with similar bandwidth and characteristic frequency selectivity. This suggests a modular organization for processing spectral bandwidth in AI.

Modular organization of frequency integration in primary auditory cortex.

Two fundamental aspects of frequency analysis shape the functional organization of primary auditory cortex. For one, the decomposition of complex sounds into different frequency components is reflected in the tonotopic organization of auditory cortical fields. Second, recent findings suggest that this decomposition is carried out in parallel for a wide range of frequency resolutions by neurons with frequency receptive fields of different sizes (bandwidths). A systematic representation of the range of frequency resolution and, equivalently, spectral integration shapes the functional organization of the iso-frequency domain. Distinct subregions, or "modules," along the iso-frequency domain can be demonstrated with various measures of spectral integration, including pure-tone tuning curves, noise masking, and electrical cochlear stimulation. This modularity in the representation of spectral integration is expressed by intrinsic cortical connections. This organization has implications for our understanding of psychophysical spectral integration measures such as the critical band and general cortical coding strategies.

Modulation of responses to optic flow in area 7a by retinotopic and oculomotor cues in monkey.

Perception of two- and three-dimensional optic flow critically depends upon extrastriate cortices that are part of the 'dorsal stream' for visual processing. Neurons in area 7a, a sub-region of the posterior parietal cortex, have a dual sensitivity to visual input and to eye position. The sensitivity and selectivity of area 7a neurons to three sensory cues - optic flow, retinotopic stimulus position and eye position - were studied. The visual response to optic flow was modulated by the retinotopic stimulus position and by the eye position in the orbit. The position dependence of the retinal and eye position modulation (i.e. gain field) were quantified by a quadratic regression model that allowed for linear or peaked receptive fields. A local maximum (or minimum) in both the retinotopic fields and the gain fields was observed, suggesting that these sensory qualities are not necessarily linearly represented in area 7a. Neurons were also found that simply encoded the eye position in the absence of optic flow. The spatial tuning for the eye position signals upon stationary stimuli and optic flow was not the same, suggesting multiple anatomical sources of the signals. These neurons can provide a substrate for spatial representation while primates move in the environment.

Analysis of optic flow in the monkey parietal area 7a.

Environmentally relevant stimuli were used to examine the selectivity of area 7a neurons to optic flow using moving, flickering dots. Monkeys performed a psychophysical task requiring them to detect changes in translation, rotational and radially structured optic flow fields consisting of collections of moving dots which are free of form cues. The neurons in area 7a were selectively responsive to all the different types of moving stimuli. Two types of tuning for motion selectivity were found. Some neurons were tuned to distinguish a particular direction of optic flow (e.g. radial expansion versus radial compression), while others were tuned to distinguish between different classes of optic flow (e.g. radial motion versus planar rotation). The latter tuning was unlike that reported for area MST by others and may represent a novel representation of optic flow. The response of these neurons to translating bars was compared to that of optic flow fields. There appeared to be no similarity in the tuning to the two types of motion. Furthermore, there does not appear to be an identity between the neurons that could be classified as opponent vector and those selective for radial optic flow. Area 7a is involved in the further analysis of optic flow beyond the cortical areas MT and MST and provides a novel representation of motion. These results are consistent with the neurons in area 7a utilizing motion for the construction of a spatial representation of extra-personal space.

The origins of aperiodicities in sensory neuron entrainment.

Aperiodic entrainment to rhythmic sensory input was obtained with either a single neuron or an excitatory network model, without addition of a stochastic or "noisy" element. The entrainment properties of primary sensory neurons were well captured by the dynamics of the Hodgkin-Huxley ordinary differential equations with a quiescent resting state or threshold for spike output. The frequency-amplitude parameter space was compressed and aperiodic regimes were small in comparison to those of periodically activated pacemaker-like neurons. Transitions between phase-locked and aperiodic entrainment patterns were predictable and determined by the equation dynamics, supporting the contention that some aperiodicities observed in situ arise from the inherent membrane properties of neurons. When the rhythmically activated neuron was embedded in an excitatory network of Hodgkin-Huxley neurons with heterogeneous synaptic delays, aperiodic entrainment patterns were more frequently encountered and these were associated with asynchronous output from the network. Embedding the rhythmically activated neuron in a network with synaptic delays greatly reduced the range of entrained spike frequencies and increased the variability in the neuronal firing. The temporal coding of sensory stimuli may be dependent on these findings. Sensory stimuli are signaled in the periphery by a mixture of periodic and irregular interspike intervals. Most models of such temporal codes assume intrinsic rhythmicity arising from the ionic currents, with variations attributed to membrane or synaptic noise. In contrast, we demonstrate irregular neural codes that arise completely in the absence of noise. In the proposed model, the sources of these irregular sensory patterns are the extensive cross-connections and resultant interactions between neurons. The balance between the regular and irregular entrainment of a neuron in situ could uniquely identify a stimulus. Other biological mechanisms of modifying the entrainment properties and promoting aperiodic entrainment are discussed.

Serotonergic suppression of interhemispheric cortical synaptic potentials.

The inhibitory effects of 5-hydroxytryptamine (5-HT) on interhemispheric and intracortical synaptic potentials in layer V neurons of the rat medial prefrontal (MFC) cortex were examined. Low concentrations (1-3 microM) of 5-HT selectively attenuated polysynaptic potentials that were similarly evoked by callosal or white matter stimulation. Maximally effective concentrations of 5-HT blocked interhemispheric transmission by 50-90%, as evidenced by an attention of the short latency callosal depolarizing synaptic potential (e-DPSP). These effects of 5-HT were not associated with a change in membrane potential or input resistance. The e-DPSP was characterized as having an N-methyl-D-aspartate (NMDA) and a non-NMDA component; the non-NMDA component was attenuated by 5-HT. Attenuation of the synaptic potential was accompanied by an attenuation of a postsynaptic glutamate potential. Suppression of both the e-DPSP and the glutamate potential was concentration dependent with 10-100 microM being maximally effective. The 5-HT1A/2 antagonist, spiperone, antagonized the effects of 5-HT on synaptic and glutamate potentials. Spiperone (1 microM) shifted the concentration-effect curves for suppression of the e-DPSP and the glutamate potential to the right; however, the Kb for the glutamate potential concentration-effect curve was 10 times that for the e-DPSP curve. The differential antagonist sensitivity of synaptic and glutamate potentials was an indication that serotonin acted on more than one receptor subtype to reduce interhemispheric transmission.

Temporal processing in the visual brain.

In conclusion these three results taken together--the single-unit data, the Gerstein and Mandelbrot model, and the modeled collection of neurons--suggest that the analysis of the temporal dynamics of neural systems can be furthered by the application of nonlinear dynamical theory. Furthermore, it appears that the range of temporal dynamics possible in visual cortex is quite broad, encompassing simple oscillations and more complex, perhaps chaotic, dynamics. Lastly, it appears that there are powerful principles at work that are leading to the organized behavior of a population of neurons. We suggest that these principles are constrained not only by the biological properties of the nervous system, but by profound mathematical principles that have already been described in many physical nonlinear systems under the aegis of chaos theory. If such constraints exist, we may have available to us mathematical and physical constructs that will allow us to study, model, and predict the behaviors of large collections of neurons that ultimately underlie the neural functioning of the brain.

Glycine potentiates NMDA responses in rat hippocampal CA1 neurons.

When superfused onto rat hippocampal slices, glycine (0.1-0.5 mM) potentiated the depolarization induced by pressure application of NMDA in normal Krebs solution and the synaptic discharge evoked by stimulation of the Schaffer collateral-commissural inputs to the CA1 pyramidal neurons bathed in Mg2+-free media; the effects were not prevented by strychnine. In addition, glycine partially reversed the blocking effect of D-2-amino-5-phosphonovalerate (AP5) on N-methyl-D-aspartate (NMDA)-induced depolarization. These results show that glycine at relatively high concentrations potentiates the NMDA-mediated response in hippocampal slices.

AHP reductions in rabbit hippocampal neurons during conditioning correlate with acquisition of the learned response.

Young adult male albino rabbits were conditioned using a free field auditory conditioned stimulus (CS) and periorbital shock unconditioned stimulus (US) in a short delay eye blink paradigm. All rabbits received two 80-trial training sessions. Intracellular recordings were made from hippocampal CA1 pyramidal neurons within brain slices prepared 24 h following the second training session. All 46 CA1 neurons included in the analysis had stable penetration, at least 70 mV impulse amplitudes and at least 40 M omega input resistance. Recording and initial data analysis were done 'blind' regarding behavioral training performance of the rabbit from which the slices were prepared. The animals were separated into a High (86 +/- 6% CRs, n = 12), and Low (12 +/- 4% CRs, n = 10) Acquisition group based on the number of blink CRs shown on the second training day (P less than 0.001). CA1 pyramidal neurons from the High Acquisition group (n = 20) showed a significant reduction in the afterhypolarization (AHP) response following 4 impulses elicited by intracellular current injection as compared to neurons from the Low Acquisition group (n = 26). The mean maximal AHP amplitudes after 4 spikes were -2.9 +/- 0.34 mV and -4.0 +/- 0.31 mV, respectively, in the High and Low Acquisition groups (P less than 0.01). The size of the AHP examined at 100 ms intervals during the first 1.7 s after the current pulse proved to be reduced in the High group both when evaluated for all points (F = 5.88, df = 1.44, P less than 0.02) and for each of the individual time points (at least P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of trimethyltin on evoked potentials in mouse hippocampal slices.

The effects of trimethyltin (TMT) on responses to orthodromic stimulation in the CA1 pyramidal cell layer and dentate gyrus were investigated in mouse hippocampal slices. In both regions exposure to 10.0 microM TMT produced an 80 to 90% reduction in population spike amplitude. Smaller decreases in spike amplitude occurred after 5 microM TMT and these effects were reversible in the pyramidial cell layer. The latency of 5.0 microM effects was longer in the dentate gyrus and were preceded by a slight (20%) increase in spike amplitude. The smallest dose of TMT tested (1.0 microM) did not change response amplitude, but did increase the occurrence of multiple population spike potentials. When TMT was applied during paired-pulse stimulation of the perforant path the potentiation of the second response was not selectively reduced. The results indicate that orthodromic excitability of both pyramidal and granule cells in the mouse hippocampus is decreased by TMT with small differences occurring in latency and reversibility at certain doses.

Effects of iontophoretic application of trimethyltin on spontaneous neuronal activity in mouse hippocampal slices.

Changes in spontaneous activity in various regions of mouse hippocampal slices were observed following iontophoretic application of trimethyltin (TMT). TMT (0.5 mM) dissolved in 0.15 M NaCl and ejected in 30 sec periods from four barrel micropipettes using anodal ejection currents (3-28 nA) produced dose dependent increases in the spontaneous activity of 67.6% of the 34 dentate gyrus cells tested. Seventy percent of the 25 CA3 cells tested displayed prolonged (30-200 sec) decreases in activity. The majority of CA1 and CA2 cells examined also displayed a decrease in firing rate. Repeated applications of TMT produced increased variability in spontaneous firing rates in all regions tested. When slices were maintained in a low Ca++, high Co++ perfusion fluid to inhibit synaptic activity, the TMT induced increase of dentate gyrus cell firing rate was not observed. The results demonstrate that direct application of TMT produces immediate changes in hippocampal cell activity that is specific for certain regions. Significant increases in firing rate were only observed in the dentate gyrus and these effects were calcium dependent.