Dorsal prefrontal and premotor cortex of the ferret as defined by distinctive patterns of thalamo-cortical projections.

Recent studies of the neurobiology of the dorsal frontal cortex (FC) of the ferret have illuminated its key role in the attention network, top-down cognitive control of sensory processing, and goal directed behavior. To elucidate the neuroanatomical regions of the dorsal FC, and delineate the boundary between premotor cortex (PMC) and dorsal prefrontal cortex (dPFC), we placed retrograde tracers in adult ferret dorsal FC anterior to primary motor cortex and analyzed thalamo-cortical connectivity. Cyto- and myeloarchitectural differences across dorsal FC and the distinctive projection patterns from thalamic nuclei, especially from the subnuclei of the medial dorsal (MD) nucleus and the ventral thalamic nuclear group, make it possible to clearly differentiate three separate dorsal FC fields anterior to primary motor cortex: polar dPFC (dPFCpol), dPFC, and PMC. Based on the thalamic connectivity, there is a striking similarity of the ferret's dorsal FC fields with other species. This possible homology opens up new questions for future comparative neuroanatomical and functional studies.

Computational Neural Modeling of Auditory Cortical Receptive Fields.

Previous studies have shown that the auditory cortex can enhance the perception of behaviorally important sounds in the presence of background noise, but the mechanisms by which it does this are not yet elucidated. Rapid plasticity of spectrotemporal receptive fields (STRFs) in the primary (A1) cortical neurons is observed during behavioral tasks that require discrimination of particular sounds. This rapid task-related change is believed to be one of the processing strategies utilized by the auditory cortex to selectively attend to one stream of sound in the presence of mixed sounds. However, the mechanism by which the brain evokes this rapid plasticity in the auditory cortex remains unclear. This paper uses a neural network model to investigate how synaptic transmission within the cortical neuron network can change the receptive fields of individual neurons. A sound signal was used as input to a model of the cochlea and auditory periphery, which activated or inhibited integrate-and-fire neuron models to represent networks in the primary auditory cortex. Each neuron in the network was tuned to a different frequency. All neurons were interconnected with excitatory or inhibitory synapses of varying strengths. Action potentials in one of the model neurons were used to calculate the receptive field using reverse correlation. The results were directly compared to previously recorded electrophysiological data from ferrets performing behavioral tasks that require discrimination of particular sounds. The neural network model could reproduce complex STRFs observed experimentally through optimizing the synaptic weights in the model. The model predicts that altering synaptic drive between cortical neurons and/or bottom-up synaptic drive from the cochlear model to the cortical neurons can account for rapid task-related changes observed experimentally in A1 neurons. By identifying changes in the synaptic drive during behavioral tasks, the model provides insights into the neural mechanisms utilized by the auditory cortex to enhance the perception of behaviorally salient sounds.

State-dependent encoding of sound and behavioral meaning in a tertiary region of the ferret auditory cortex.

In higher sensory cortices, there is a gradual transformation from sensation to perception and action. In the auditory system, this transformation is revealed by responses in the rostral ventral posterior auditory field (VPr), a tertiary area in the ferret auditory cortex, which shows long-term learning in trained compared to naïve animals, arising from selectively enhanced responses to behaviorally relevant target stimuli. This enhanced representation is further amplified during active performance of spectral or temporal auditory discrimination tasks. VPr also shows sustained short-term memory activity after target stimulus offset, correlated with task response timing and action. These task-related changes in auditory filter properties enable VPr neurons to quickly and nimbly switch between different responses to the same acoustic stimuli, reflecting either spectrotemporal properties, timing, or behavioral meaning of the sound. Furthermore, they demonstrate an interaction between the dynamics of short-term attention and long-term learning, as incoming sound is selectively attended, recognized, and translated into action.

Laminar profile of task-related plasticity in ferret primary auditory cortex.

Rapid task-related plasticity is a neural correlate of selective attention in primary auditory cortex (A1). Top-down feedback from higher-order cortex may drive task-related plasticity in A1, characterized by enhanced neural representation of behaviorally meaningful sounds during auditory task performance. Since intracortical connectivity is greater within A1 layers 2/3 (L2/3) than in layers 4-6 (L4-6), we hypothesized that enhanced representation of behaviorally meaningful sounds might be greater in A1 L2/3 than L4-6. To test this hypothesis and study the laminar profile of task-related plasticity, we trained 2 ferrets to detect pure tones while we recorded laminar activity across a 1.8 mm depth in A1. In each experiment we analyzed high-gamma local field potentials (LFPs) and multi-unit spiking in response to identical acoustic stimuli during both passive listening and active task performance. We found that neural responses to auditory targets were enhanced during task performance, and target enhancement was greater in L2/3 than in L4-6. Spectrotemporal receptive fields (STRFs) computed from both high-gamma LFPs and multi-unit spiking showed similar increases in auditory target selectivity, also greatest in L2/3. Our results suggest that activity within intracortical networks plays a key role in the underlying neural mechanisms of selective attention.

Go/No-Go task engagement enhances population representation of target stimuli in primary auditory cortex.

Primary sensory cortices are classically considered to extract and represent stimulus features, while association and higher-order areas are thought to carry information about stimulus meaning. Here we show that this information can in fact be found in the neuronal population code of the primary auditory cortex (A1). A1 activity was recorded in awake ferrets while they either passively listened or actively discriminated stimuli in a range of Go/No-Go paradigms, with different sounds and reinforcements. Population-level dimensionality reduction techniques reveal that task engagement induces a shift in stimulus encoding from a sensory to a behaviorally driven representation that specifically enhances the target stimulus in all paradigms. This shift partly relies on task-engagement-induced changes in spontaneous activity. Altogether, we show that A1 population activity bears strong similarities to frontal cortex responses. These findings indicate that primary sensory cortices implement a crucial change in the structure of population activity to extract task-relevant information during behavior.

Stronger efferent suppression of cochlear neural potentials by contralateral acoustic stimulation in awake than in anesthetized chinchilla.

There are two types of sensory cells in the mammalian cochlea, inner hair cells, which make synaptic contact with auditory-nerve afferent fibers, and outer hair cells that are innervated by crossed and uncrossed medial olivocochlear (MOC) efferent fibers. Contralateral acoustic stimulation activates the uncrossed efferent MOC fibers reducing cochlear neural responses, thus modifying the input to the central auditory system. The chinchilla, among all studied mammals, displays the lowest percentage of uncrossed MOC fibers raising questions about the strength and frequency distribution of the contralateral-sound effect in this species. On the other hand, MOC effects on cochlear sensitivity have been mainly studied in anesthetized animals and since the MOC-neuron activity depends on the level of anesthesia, it is important to assess the influence of anesthesia in the strength of efferent effects. Seven adult chinchillas (Chinchilla laniger) were chronically implanted with round-window electrodes in both cochleae. We compared the effect of contralateral sound in awake and anesthetized condition. Compound action potentials (CAP) and cochlear microphonics (CM) were measured in the ipsilateral cochlea in response to tones in absence and presence of contralateral sound. Control measurements performed after middle-ear muscles section in one animal discarded any possible middle-ear reflex activation. Contralateral sound produced CAP amplitude reductions in all chinchillas, with suppression effects greater by about 1-3 dB in awake than in anesthetized animals. In contrast, CM amplitude increases of up to 1.9 dB were found in only three awake chinchillas. In both conditions the strongest efferent effects were produced by contralateral tones at frequencies equal or close to those of ipsilateral tones. Contralateral CAP suppressions for 1-6 kHz ipsilateral tones corresponded to a span of uncrossed MOC fiber innervation reaching at least the central third of the chinchilla cochlea.

Emergent selectivity for task-relevant stimuli in higher-order auditory cortex.

A variety of attention-related effects have been demonstrated in primary auditory cortex (A1). However, an understanding of the functional role of higher auditory cortical areas in guiding attention to acoustic stimuli has been elusive. We recorded from neurons in two tonotopic cortical belt areas in the dorsal posterior ectosylvian gyrus (dPEG) of ferrets trained on a simple auditory discrimination task. Neurons in dPEG showed similar basic auditory tuning properties to A1, but during behavior we observed marked differences between these areas. In the belt areas, changes in neuronal firing rate and response dynamics greatly enhanced responses to target stimuli relative to distractors, allowing for greater attentional selection during active listening. Consistent with existing anatomical evidence, the pattern of sensory tuning and behavioral modulation in auditory belt cortex links the spectrotemporal representation of the whole acoustic scene in A1 to a more abstracted representation of task-relevant stimuli observed in frontal cortex.

Auditory cortex basal activity modulates cochlear responses in chinchillas.

BACKGROUND: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. METHODOLOGY/PRINCIPAL FINDINGS: Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. CONCLUSIONS/SIGNIFICANCE: These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects suggests that there are at least two functional pathways from the auditory cortex to the cochlea.

Effects of electrical stimulation of olivocochlear fibers in cochlear potentials in the chinchilla.

The mammalian cochlea has two types of sensory cells; inner hair cells, which receive auditory-nerve afferent innervation, and outer hair cells, innervated by efferent axons of the medial olivocochlear (MOC) system. The role of the MOC system in hearing is still controversial. Recently, by recording cochlear potentials in behaving chinchillas, we suggested that one of the possible functions of the efferent system is to reduce cochlear sensitivity during attention to other sensory modalities (Delano et al. in J Neurosci 27:4146-4153, 2007). However, in spite of these compelling results, the physiological effects of electrical MOC activation on cochlear potentials have not been described in detail in chinchillas. The main objective of the present work was to describe these efferent effects in the chinchilla, comparing them with those in other species and in behavioral experiments. We activated the MOC efferent axons in chinchillas with sectioned middle-ear muscles by applying current pulses at the fourth-ventricle floor. Auditory-nerve compound action potentials (CAP) and cochlear microphonics (CM) were acquired in response to clicks and tones of several frequencies, using a round-window electrode. Electrical efferent stimulation produced CAP amplitude suppressions reaching up to 11 dB. They were higher for low to moderate sound levels. Additionally, CM amplitude increments were found, the largest (≤ 2.5 dB) for low intensity tones. CAP suppression was present at all stimulus frequencies, but was greatest for 2 kHz. CM increments were highest for low-frequency tones, and almost absent at high frequencies. We conclude that the effect obtained in chinchilla is similar to but smaller than that observed in cats, and that the effects seen in awake chinchillas, albeit different in magnitude, are consistent with the activation of efferent fibers.

A visual cue modulates the firing rate and latency of auditory-cortex neurons in the chinchilla.

We studied single and multi-unit activity recorded with tetrodes, from the left auditory cortex of awake chinchillas while they performed a frequency discrimination task. Auditory stimuli were preceded by a silent visual cue. We examined firing rates and first-spike latencies of 181 units in the presence and absence of the visual cue. To discard possible auditory artifacts produced by the visual cue, cochlear potentials were simultaneously recorded by an electrode positioned at the round window of the right cochlea. We found that the visual stimulus altered the firing rate and the mean first-spike latency of 9% and 18% of the recorded auditory-cortex cells, respectively. Furthermore, we found that the subset of neurons in which the firing rate was modulated by the visual cue was distinct from the subset of neurons that changed their latency in the presence of the visual cue. Adding both groups, a visual-stimulus modulated the firing characteristics of 27% of the recorded auditory-cortex neurons in the awake chinchilla. Our results imply that in the auditory cortex, latency and firing rate can be independently altered by visual stimuli, and that both types of analysis must be considered in order to fully understand neural cross-modal interactions.

Selective attention to visual stimuli reduces cochlear sensitivity in chinchillas.

It is generally accepted that during periods of attention to specific stimuli there are changes in the neural activity of central auditory structures; however, it is controversial whether attention can modulate auditory responses at the cochlear level. Several studies performed in animals as well as in humans have attempted to find a modulation of cochlear responses during visual attention with contradictory results. Here, we have appraised cochlear sensitivity in behaving chinchillas by measuring, with a chronically implanted round-window electrode, sound-evoked auditory-nerve compound action potentials and cochlear microphonics, a measure of outer hair cell function, during selective attention to visual stimuli. Chinchillas were trained in a visual discrimination or in an auditory frequency discrimination two-choice task. We found a significant decrease of cochlear sensitivity during the period of attention to visual stimuli in the animals performing the visual discrimination task, but not in those performing the auditory task, demonstrating that this physiological effect is related to selective attention to visual stimuli rather than to an increment in arousal level. Furthermore, the magnitude of the cochlear-sensitivity reductions increased in sessions performed with shorter target-light durations (4-0.5 s), suggesting that this effect is stronger for higher attentional demands of the task. These results demonstrate that afferent auditory activity is modulated by selective attention as early as at sensory transduction, possibly through activation of olivocochlear efferent fibers.