Auditory motion does not modulate spiking activity in the middle temporal and medial superior temporal visual areas.

The integration of multiple sensory modalities is a key aspect of brain function, allowing animals to take advantage of concurrent sources of information to make more accurate perceptual judgments. For many years, multisensory integration in the cerebral cortex was deemed to occur only in high-level "polysensory" association areas. However, more recent studies have suggested that cross-modal stimulation can also influence neural activity in areas traditionally considered to be unimodal. In particular, several human neuroimaging studies have reported that extrastriate areas involved in visual motion perception are also activated by auditory motion, and may integrate audiovisual motion cues. However, the exact nature and extent of the effects of auditory motion on the visual cortex have not been studied at the single neuron level. We recorded the spiking activity of neurons in the middle temporal (MT) and medial superior temporal (MST) areas of anesthetized marmoset monkeys upon presentation of unimodal stimuli (moving auditory or visual patterns), as well as bimodal stimuli (concurrent audiovisual motion). Despite robust, direction selective responses to visual motion, none of the sampled neurons responded to auditory motion stimuli. Moreover, concurrent moving auditory stimuli had no significant effect on the ability of single MT and MST neurons, or populations of simultaneously recorded neurons, to discriminate the direction of motion of visual stimuli (moving random dot patterns with varying levels of motion noise). Our findings do not support the hypothesis that direct interactions between MT, MST and areas low in the hierarchy of auditory areas underlie audiovisual motion integration.

Immediate and Medium-term Changes in Cortical and Hippocampal Inhibitory Neuronal Populations after Diffuse TBI.

Changes in inhibition following traumatic brain injury (TBI) appear to be one of the major factors that contribute to excitation:inhibition imbalance. Neuron pathology, interneurons in particular evolves from minutes to weeks post injury and follows a complex time course. Previously, we showed that in the long-term in diffuse TBI (dTBI), there was select reduction of specific dendrite-targeting neurons in sensory cortex and hippocampus while in motor cortex there was up-regulation of specific dendrite-targeting neurons. We now investigated the time course of dTBI effects on interneurons in neocortex and hippocampus. Brains were labeled with antibodies against calbindin (CB), parvalbumin (PV), calretinin (CR) neuropeptide Y (NPY), and somatostatin (SOM) at 24 h and 2 weeks post dTBI. We found time-dependent, brain area-specific changes in inhibition at 24 h and 2 weeks. At 24 h post-injury, reduction of dendrite-targeting inhibitory neurons occurred in sensory cortex and hippocampus. At 2 weeks, we found compensatory changes in the somatosensory cortex and CA2/3 of hippocampus affected at 24 h, with affected interneuronal populations returning to sham levels. However, DG of hippocampus now showed reduction of dendrite-targeting inhibitory neurons. Finally, with respect to motor cortex, there was an upregulation of dendrite-targeting interneurons in the supragranular layers at 24 h returning to normal levels by 2 weeks. Overall, our findings reconfirm that dendritic inhibition is particularly susceptible to brain trauma, but also show that there are complex brain-area-specific changes in inhibitory neuronal numbers and in compensatory changes, rather than a simple monotonic progression of changes post-dTBI.

Neuronal Correlations in MT and MST Impair Population Decoding of Opposite Directions of Random Dot Motion.

The study of neuronal responses to random-dot motion patterns has provided some of the most valuable insights into how the activity of neurons is related to perception. In the opposite directions of motion paradigm, the motion signal strength is decreased by manipulating the coherence of random dot patterns to examine how well the activity of single neurons represents the direction of motion. To extend this paradigm to populations of neurons, studies have used modelling based on data from pairs of neurons, but several important questions require further investigation with larger neuronal datasets. We recorded neuronal populations in the middle temporal (MT) and medial superior temporal (MST) areas of anaesthetized marmosets with electrode arrays, while varying the coherence of random dot patterns in two opposite directions of motion (left and right). Using the spike rates of simultaneously recorded neurons, we decoded the direction of motion at each level of coherence with linear classifiers. We found that the presence of correlations had a detrimental effect to decoding performance, but that learning the correlation structure produced better decoding performance compared to decoders that ignored the correlation structure. We also found that reducing motion coherence increased neuronal correlations, but decoders did not need to be optimized for each coherence level. Finally, we showed that decoder weights depend of left-right selectivity at 100% coherence, rather than the preferred direction. These results have implications for understanding how the information encoded by populations of neurons is affected by correlations in spiking activity.

Progesterone Sharpens Temporal Response Profiles of Sensory Cortical Neurons in Animals Exposed to Traumatic Brain Injury.

Traumatic brain injury (TBI) initiates a cascade of pathophysiological changes that are both complex and difficult to treat. Progesterone (P4) is a neuroprotective treatment option that has shown excellent preclinical benefits in the treatment of TBI, but these benefits have not translated well in the clinic. We have previously shown that P4 exacerbates the already hypoactive upper cortical responses in the short-term post-TBI and does not reduce upper cortical hyperactivity in the long term, and we concluded that there is no tangible benefit to sensory cortex firing strength. Here we examined the effects of P4 treatment on temporal coding resolution in the rodent sensory cortex in both the short term (4 d) and long term (8 wk) following impact-acceleration-induced TBI. We show that in the short-term postinjury, TBI has no effect on sensory cortex temporal resolution and that P4 also sharpens the response profile in all cortical layers in the uninjured brain and all layers other than layer 2 (L2) in the injured brain. In the long term, TBI broadens the response profile in all cortical layers despite firing rate hyperactivity being localized to upper cortical layers and P4 sharpens the response profile in TBI animals in all layers other than L2 and has no long-term effect in the sham brain. These results indicate that P4 has long-term effects on sensory coding that may translate to beneficial perceptual outcomes. The effects seen here, combined with previous beneficial preclinical data, emphasize that P4 is still a potential treatment option in ameliorating TBI-induced disorders.

Laminar-specific encoding of texture elements in rat barrel cortex.

KEY POINTS: For rats texture discrimination is signalled by the large face whiskers by stick-slip events. Neural encoding of repetitive stick-slip events will be influenced by intrinsic properties of adaptation. We show that texture coding in the barrel cortex is laminar specific and follows a power function. Our results also show layer 2 codes for novel feature elements via robust firing rates and temporal fidelity. We conclude that texture coding relies on a subtle neural ensemble to provide important object information. ABSTRACT: Texture discrimination by rats is exquisitely guided by fine-grain mechanical stick-slip motions of the face whiskers as they encounter, stick to and slip past successive texture-defining surface features such as bumps and grooves. Neural encoding of successive stick-slip texture events will be shaped by adaptation, common to all sensory systems, whereby receptor and neural responses to a stimulus are affected by responses to preceding stimuli, allowing resetting to signal novel information. Additionally, when a whisker is actively moved to contact and brush over surfaces, that motion itself generates neural responses that could cause adaptation of responses to subsequent stick-slip events. Nothing is known about encoding in the rat whisker system of stick-slip events defining textures of different grain or the influence of adaptation from whisker protraction or successive texture-defining stick-slip events. Here we recorded responses from halothane-anaesthetized rats in response to texture-defining stimuli applied to passive whiskers. We demonstrate that: across the columnar network of the whisker-recipient barrel cortex, adaptation in response to repetitive stick-slip events is strongest in uppermost layers and equally lower thereafter; neither whisker protraction speed nor stick-slip frequency impede encoding of stick-slip events at rates up to 34.08 Hz; and layer 2 normalizes responses to whisker protraction to resist effects on texture signalling. Thus, within laminar-specific response patterns, barrel cortex reliably encodes texture-defining elements even to high frequencies.

Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments.NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural basis of motion perception in the marmoset, a small primate species that is becoming increasingly popular as an experimental model.

Hypo-excitation across all cortical laminae defines intermediate stages of cortical neuronal dysfunction in diffuse traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality world-wide and can result in persistent cognitive, sensory and behavioral dysfunction. Understanding the time course of TBI-induced pathology is essential to effective treatment outcomes. We induced TBI in rats using an impact acceleration method and tested for sensorimotor skill and sensory sensitivity behaviors for two weeks to find persistently poor outcomes post-injury. At two weeks post-injury we made high resolution extracellular recordings from barrel cortex neurons, to simple and complex whisker deflections. We found that the supragranular suppression of neural firing (compared to normal) previously seen in the immediate post-TBI aftermath had spread to include suppression of input and infragranular layers at two weeks post-injury; thus, there was suppression of whisker-driven firing rates in all cortical layers to both stimulus types. Further, there were abnormalities in temporal response patterns such that in layers 3-5 there was a temporal broadening of response patterns in response to both whisker deflection stimulus types and in L2 a narrowing of temporal patterns in response to the complex stimulus. Thus, at two weeks post-TBI, supragranular hypo-excitation has evolved to include deep cortical layers likely as a function of progressive atrophy and neurodegeneration. These results are consistent with the hypothesis that TBI alters the delicate excitatory/inhibitory balance in cortex and likely contributes to temporal broadening of responses and restricts the ability to code for complex sensory stimuli.

Progesterone Exacerbates Short-Term Effects of Traumatic Brain Injury on Supragranular Responses in Sensory Cortex and Over-Excites Infragranular Responses in the Long Term.

Progesterone (P4) has been suggested as a neuroprotective agent for traumatic brain injury (TBI) because it ameliorates many post-TBI sequelae. We examined the effects of P4 treatment on the short-term (4 days post-TBI) and long-term (8 weeks post-TBI) aftermath on neuronal processing in the rodent sensory cortex of impact acceleration-induced diffuse TBI. We have previously reported that in sensory cortex, diffuse TBI induces a short-term hypoexcitation that is greatest in the supragranular layers and decreases with depth, but a long-term hyperexcitation that is exclusive to the supragranular layers. Now, adult male TBI-treated rats administered P4 showed, in the short term, even greater suppression in neural responses in supragranular layers but a reversal of the TBI-induced suppression in granular and infragranular layers. In long-term TBI there were only inconsistent effects of P4 on the TBI-induced hyperexcitation in supragranular responses but infragranular responses, which were not affected by TBI alone, were elevated by P4 treatment. Intriguingly, the effects in the injured brain were almost identical to P4 effects in the normal brain, as seen in sham control animals treated with P4: in the short term, P4 effects in the normal brain were identical to those exercised in the injured brain and in the long term, P4 effects in the normal brain were rather similar to what was seen in the TBI brain. Overall, these results provide no support for any protective effects of P4 treatment on neuronal encoding in diffuse TBI, and this was reflected in sensorimotor and other behavior tasks also tested here. Additionally, the effects suggest that mechanisms used for P4 effects in the normal brain are also intact in the injured brain.