Publications using TDT

Basal forebrain modulation of central circuits is associated with active sensation, attention, and learning. While cholinergic modulations have been studied extensively the effect of non-cholinergic basal forebrain subpopulations on sensory processing remains largely unclear. Here, we directly compare optogenetic manipulation effects of two major basal forebrain subpopulations on principal neuron activity in an early sensory processing area, i.e. mitral/tufted cells (MTCs) in the olfactory bulb. In contrast to cholinergic projections, which consistently increased MTC firing, activation of GABAergic fibers from basal forebrain to the olfactory bulb leads to differential modulation effects: while spontaneous MTC activity is mainly inhibited, odor-evoked firing is predominantly enhanced. Moreover, sniff-triggered averages revealed an enhancement of maximal sniff evoked firing amplitude and an inhibition of firing rates outside the maximal sniff phase. These findings demonstrate that GABAergic neuromodulation affects MTC firing in a bimodal, sensory-input dependent way, suggesting that GABAergic basal forebrain modulation could be an important factor in attention mediated filtering of sensory information to the brain.

Proprioceptive feedback is a critical component of voluntary movement planning and execution. Neuroprosthetic technologies aiming at restoring movement must interact with it to restore accurate motor control. Optimization and design of such technologies depends on the availability of quantitative insights into the neural dynamics of proprioceptive afferents during functional movements. However, recording proprioceptive neural activity during unconstrained movements in clinically relevant animal models presents formidable challenges. In this work, we developed a computational framework to estimate the spatiotemporal patterns of proprioceptive inputs to the cervical spinal cord during three-dimensional arm movements in monkeys. We extended a biomechanical model of the monkey arm with ex-vivo measurements, and combined it with models of mammalian group-Ia, Ib and II afferent fibers. We then used experimental recordings of arm kinematics and muscle activity of two monkeys performing a reaching and grasping task to estimate muscle stretches and forces with computational biomechanics. Finally, we projected the simulated proprioceptive firing rates onto the cervical spinal roots, thus obtaining spatiotemporal maps of spinal proprioceptive inputs during voluntary movements. Estimated maps show complex and markedly distinct patterns of neural activity for each of the fiber populations spanning the spinal cord rostro-caudally. Our results indicate that reproducing the proprioceptive information flow to the cervical spinal cord requires complex spatio-temporal modulation of each spinal root. Our model can support the design of neuroprosthetic technologies as well as in-silico investigations of the primate sensorimotor system.

Amphibians are unique among extant vertebrates in having middle ear cavities that are internally coupled to each other and to the lungs. In frogs, the lung-to-ear sound transmission pathway can influence the tympanum’s inherent directionality, but what role such effects might play in directional hearing remain unclear. In this study of the American green treefrog ( Hyla cinerea ), we tested the hypothesis that the lung-to-ear sound transmission pathway functions to improve directional hearing, particularly in the context of interspecific sexual communication. Using laser vibrometry, we measured the tympanum’s vibration amplitude in females in response to a frequency modulated sweep presented from 12 sound incidence angles in azimuth. Tympanum directionality was determined across three states of lung inflation (inflated, deflated, reinflated) both for a single tympanum in the form of the vibration amplitude difference (VAD) and for binaural comparisons in the form of the interaural vibration amplitude difference (IVAD). The state of lung inflation had negligible effects (typically less than 0.5 dB) on both VADs and IVADs at frequencies emphasized in the advertisement calls produced by conspecific males (834 Hz and 2730 Hz). Directionality at the peak resonance frequency of the lungs (1558 Hz) was improved by ≅ 3 dB for a single tympanum when the lungs were inflated versus deflated, but IVADs were not impacted by the state of lung inflation. Based on these results, we reject the hypothesis that the lung-to-ear sound transmission pathway functions to improve directional hearing in frogs. SUMMARY STATEMENT Contrary to prevailing views on the mechanisms of hearing in frogs, the lung-to-ear pathway for sound transmission does not improve directional hearing in these vociferous vertebrates.

The ventral tegmental area (VTA) has dopamine, GABA, and glutamate neurons, which have been implicated in reward and aversion. Here, we determined whether VTA-glutamate or -GABA neurons play a role in innate defensive behavior. By VTA cell-type-specific genetic ablation, we found that ablation of glutamate, but not GABA, neurons abolishes escape behavior in response to threatening stimuli. We found that escape behavior is also decreased by chemogenetic inhibition of VTA-glutamate neurons and detected increases in activity in VTA-glutamate neurons in response to the threatening stimuli. By ultrastructural and electrophysiological analysis, we established that VTA-glutamate neurons receive a major monosynaptic glutamatergic input from the lateral hypothalamic area (LHA) and found that photoinhibition of this input decreases escape responses to threatening stimuli. These findings indicate that VTA-glutamate neurons are activated by and required for innate defensive responses and that information on threatening stimuli to VTA-glutamate neurons is relayed by LHA-glutamate neurons.

Odors are well known to elicit strong emotional and behavioral responses that become strengthened throughout learning, yet the specific cellular systems involved in odor learning and the direct influence of these on behavior are unclear. Here, we investigate the representation of odor-reward associations within two areas recipient of dense olfactory input, the posterior piriform cortex (pPCX) and the olfactory tubercle (OT), using electrophysiological recordings from mice engaged in reward-based learning. Neurons in both regions represent conditioned odors and do so with similar information content, yet the proportion of neurons recruited by conditioned rewarded odors and the magnitudes and durations of their responses are greater in the OT. Using fiber photometry, we find that OT D1-type dopamine-receptor-expressing neurons flexibly represent odors based on reward associations, and using optogenetics, we show that these neurons influence behavioral engagement. These findings contribute to a model whereby OT D1 neurons support odor-guided motivated behaviors.

Traumatic stress can lead to heightened aggression which may be a symptom of psychiatric diseases such as PTSD and intermittent explosive disorder. The medial amygdala (MeA) is an evolutionarily conserved subnucleus of the amygdala that regulates attack behavior and behavioral responses to stressors. The precise contribution of the MeA in traumatic stress-induced aggression, however, requires further elucidation. In this study, we used foot shock to induce traumatic stress in mice and examine the mechanisms of prolonged aggression increase associated with it. Foot shock causes a prolonged increase in aggression that lasts at least one week. In vivo electrophysiological recordings revealed that foot shock induces potentiation of synapses formed between the MeA and the ventromedial hypothalamus (VmH) and bed nucleus of the stria terminalis (BNST). This synaptic potentiation lasts at least one week. Induction of synaptic depotentiation with low-frequency photostimulation (LFPS) immediately after foot shock suppresses the prolonged aggression increase without affecting non-aggressive social behavior, anxiety-like and depression-like behaviors, or fear learning. These results show that potentiation of the MeA-VmH and MeA-BNST circuits is essential for traumatic stress to cause a prolonged increase in aggression. These circuits may be potential targets for the development of therapeutic strategies to treat the aggression symptom associated with psychiatric diseases.

In vivo loose patch and breakthrough whole-cell recordings are useful tools for investigating the intrinsic and synaptic properties of neurons. However, the correlation among pipette resistance, seal condition, and recording time is not thoroughly clear. Presently, we investigated the recording time of different pipette resistances and seal conditions in loose patch and breakthrough whole-cell recordings. The recording time did not change with pipette resistance for loose patch recording (Rp-loose) and first increased and then decreased as seal resistance for loose patch recording (Rs-loose) increased. For a high probability of a recording time ≥30 min, the low and high cutoff values of Rs-loose were 21.5 and 36 MΩ, respectively. For neurons with Rs-loose values of 21.5-36 MΩ, the action potential (AP) amplitudes changed slightly 30 min after the seal. The recording time increased as seal resistance for whole-cell recording (Rs-tight) increased and the zero-current membrane potential for breakthrough whole-cell recording (MPzero-current) decreased. For a high probability of a recording time ≥30 min, the cutoff values of Rs-tight and MPzero-current were 2.35 GΩ and -53.5 mV, respectively. The area under the curve (AUC) of the MPzero-current receiver operating characteristic (ROC) curve was larger than that of the Rs-tight ROC curve. For neurons with MPzero-current values ≤ -53.5 mV, the inhibitory or excitatory postsynaptic current amplitudes did not show significant changes 30 min after the seal. In neurons with Rs-tight values ≥2.35 GΩ, the recording time gradually increased and then decreased as the pipette resistance for whole-cell recording (Rp-tight) increased. For the high probability of a recording time ≥30 min, the low and high cutoff values of Rp-tight were 6.15 and 6.45 MΩ, respectively. Together, we concluded that the optimal Rs-loose range is 21.5-36 MΩ, the optimal Rp-tight range is 6.15-6.45 MΩ, and the optimal Rs-tight and MPzero-current values are ≥2.35 GΩ and ≤ -53.5 mV, respectively. Compared with Rs-tight, the MPzero-current value can more accurately discriminate recording times ≥30 min and <30 min.

2-Hydroxypropyl-β-cyclodextrin (HPβCD), a cholesterol chelator, is being used to treat diseases associated with abnormal cholesterol metabolism such as Niemann-Pick C1 (NPC1). However, the high doses of HPβCD needed to slow disease progression may cause hearing loss. Previous studies in mice have suggested that HPβCD ototoxicity results from selective outer hair cell (OHC) damage. However, it is unclear if HPβCD causes the same type of damage or is more or less toxic to other species such as rats, which are widely used in toxicity research. To address these issues, rats were given a subcutaneous injection of HPβCD between 500 and 4000 mg/kg. Distortion product otoacoustic emissions (DPOAE), the cochlear summating potential (SP), and compound action potential (CAP) were used to assess cochlear function followed by quantitative analysis of OHC and inner hair cell (IHC) loss. The 3000- and 4000-mg/kg doses abolished DPOAE and greatly reduced SP and CAP amplitudes. These functional deficits were associated with nearly complete loss of OHC as well as ~ 80% IHC loss over the basal two thirds of the cochlea. The 2000-mg/kg dose abolished DPOAE and significantly reduced SP and CAP amplitudes at the high frequencies. These deficits were linked to OHC and IHC losses in the high-frequency region of the cochlea. Little or no damage occurred with 500 or 1000 mg/kg of HPβCD. The HPβCD-induced functional and structural deficits in rats occurred suddenly, involved damage to both IHC and OHC, and were more severe than those reported in mice.

Auditory dysfunction is the most prevalent injury associated with blast overpressure exposure (BOP) in Warfighters and civilians, yet little is known about the underlying pathophysiological mechanisms. To gain insights into these injuries, an advanced blast simulator was used to expose rats to BOP and assessments were made to identify structural and molecular changes in the middle/inner ears utilizing otoscopy, RNA sequencing (RNA-seq), and histopathological analysis. Deficits persisting up to 1 month after blast exposure were observed in the distortion product otoacoustic emissions (DPOAEs) and the auditory brainstem responses (ABRs) across the entire range of tested frequencies (4–40 kHz). During the recovery phase at sub-acute time points, low frequency (e.g. 4–8 kHz) hearing improved relatively earlier than for high frequency (e.g. 32–40 kHz). Perforation of tympanic membranes and middle ear hemorrhage were observed at 1 and 7 days, and were restored by day 28 post-blast. A total of 1,158 differentially expressed genes (DEGs) were significantly altered in the cochlea on day 1 (40% up-regulated and 60% down-regulated), whereas only 49 DEGs were identified on day 28 (63% up-regulated and 37% down-regulated). Seven common DEGs were identified at both days 1 and 28 following blast, and are associated with inner ear mechanotransduction, cytoskeletal reorganization, myelin development and axon survival. Further studies on altered gene expression in the blast-injured rat cochlea may provide insights into new therapeutic targets and approaches to prevent or treat similar cases of blast-induced auditory damage in human subjects.

Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e., increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two‐photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10‐Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.

Our understanding of nonlinear stimulus transformations by neural circuits is hindered by the lack of comprehensive yet interpretable computational modeling frameworks. Here, we propose a data-driven approach based on deep neural networks to directly model arbitrarily nonlinear stimulus-response mappings. Reformulating the exact function of a trained neural network as a collection of stimulus-dependent linear functions enables a locally linear receptive field interpretation of the neural network. Predicting the neural responses recorded invasively from the auditory cortex of neurosurgical patients as they listened to speech, this approach significantly improves the prediction accuracy of auditory cortical responses, particularly in nonprimary areas. Moreover, interpreting the functions learned by neural networks uncovered three distinct types of nonlinear transformations of speech that varied considerably from primary to nonprimary auditory regions. The ability of this framework to capture arbitrary stimulus-response mappings while maintaining model interpretability leads to a better understanding of cortical processing of sensory signals.

The mechanical mismatch between implantable interfaces and neural tissues may be reduced by employing soft polymeric materials. Here, we report on a simple strategy to prepare and pattern a soft electrode coating of neural interfacing devices based on a screen-printable conducting hydrogel. The coating formulation, based on polyacrylamide and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, is suitable to additive manufacturing and exhibits excellent adhesion to polydimethylsiloxane, an elastomer commonly used as a substrate in soft neural interfaces. The soft conductive coating displays a tunable elastic modulus in the 10–100 kPa range and electrochemical properties on a par with stiff conductive inks while supporting good neural cell attachment and proliferation in vitro. Next, the soft printable hydrogel is integrated within a 4 × 4 microelectrode array for electrocorticography with 250 μm-diameter contacts. Acute recording of cortical local field potentials and electrochemical characterization preimplantation and postimplantation highlight the stability of the soft organic conductor. The overall robustness of the soft coating and its patterning method provide a promising route for a range of implantable bioelectronic applications.

Repeated stimulus presentations commonly produce decreased neural responses—a phenomenon known as repetition suppression (RS) or adaptation—in ventral temporal cortex (VTC) of humans and nonhuman primates. However, the temporal features of RS in human VTC are not well understood. To fill this gap in knowledge, we utilized the precise spatial localization and high temporal resolution of electrocorticography (ECoG) from nine human subjects implanted with intracranial electrodes in the VTC. The subjects viewed nonrepeated and repeated images of faces with long-lagged intervals and many intervening stimuli between repeats. We report three main findings: 1) robust RS occurs in VTC for activity in high-frequency broadband (HFB), but not lower-frequency bands; 2) RS of the HFB signal is associated with lower peak magnitude (PM), lower total responses, and earlier peak responses; and 3) RS effects occur early within initial stages of stimulus processing and persist for the entire stimulus duration. We discuss these findings in the context of early and late components of visual perception, as well as theoretical models of repetition suppression.

Cisplatin is a widely used anti-cancer drug used to treat a variety of cancer types. One of the side effects of this life-saving drug is irreversible ototoxicity, resulting in permanent hearing loss in many patients. In order to understand why cisplatin is particularly toxic to the inner ear, we compared the hearing loss and cochlear uptake of cisplatin to that of two related drugs, carboplatin and oxaliplatin. These three drugs are similar in that each contains a core platinum atom; however, carboplatin and oxaliplatin are considered less ototoxic than cisplatin. We delivered these three drugs to mice using a 6-week cyclic drug administration protocol. We performed the experiment twice, once using equimolar concentrations of the drugs and once using concentrations of the drugs more proportional to those used in the clinic. For both concentrations, we detected a significant hearing loss caused by cisplatin and no hearing loss caused by carboplatin or oxaliplatin. Cochlear uptake of each drug was measured using inductively coupled plasma mass spectrometry (ICP-MS) to detect platinum. Cochlear platinum levels were highest in mice treated with cisplatin followed by oxaliplatin, while carboplatin was largely excluded from the cochlea. Even when the drug doses were increased, cochlear platinum remained low in mice treated with oxaliplatin or carboplatin. We also examined drug clearance from the inner ear by measuring platinum levels at 1 h and 24 h after drug administration. Our findings suggest that the reduced cochlear platinum we observed with oxaliplatin and carboplatin were not due to increased clearance of these drugs relative to cisplatin. Taken together, our data indicate that the differential ototoxicity among cisplatin, carboplatin, and oxaliplatin is attributable to differences in cochlear uptake of these three drugs.

Understanding the mechanisms by which neuronal population activity gives rise to perception and behavior remains a central question in systems neuroscience. Such understanding is complicated by the fact that natural stimuli often have complex structure. Here we investigated how heterogeneities within a sensory neuron population influence the coding of a noisy stimulus waveform (i.e., the noise) and its behaviorally relevant envelope signal (i.e., the signal). We found that On- and Off-type neurons displayed more heterogeneities in their responses to the noise than in their responses to the signal. These differences in heterogeneities had important consequences when quantifying response similarity between pairs of neurons. Indeed, the larger response heterogeneity displayed by On- and Off-type neurons made their pairwise responses to the noise on average more independent than when instead considering pairs of On-type or Off-type neurons. Such relative independence allowed for better averaging out of the noise response when pooling neural activities in a mixed-type (i.e., On- and Off-type) than for same-type (i.e., only On-type or only Off-type), thereby leading to greater information transmission about the signal. Our results thus reveal a function for the combined activities of On- and Off-type neurons towards improving information transmission of envelope stimuli at the population level. Our results will likely generalize because natural stimuli across modalities are characterized by a stimulus waveform whose envelope varies independently as well as because On- and Off-type neurons are observed across systems and species.

Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned PEs, which report surprise during sensory processing. But mounting theoretical accounts from the predictive processing framework postulate that dopamine, as a neuromodulator, could potentially regulate the postsynaptic gain of sensory neurons, thereby scaling unsigned PEs according to their expected precision or confidence. Despite ample modeling work, the physiological effects of dopamine on the processing of surprising sensory information are yet to be addressed experimentally. In this study, we tested how dopamine modulates midbrain processing of unexpected tones. We recorded extracellular responses from the rat inferior colliculus to oddball and cascade sequences, before, during, and after the microiontophoretic application of dopamine or eticlopride (a D2-like receptor antagonist). Results demonstrate that dopamine reduces the net neuronal responsiveness exclusively to unexpected sensory input without significantly altering the processing of expected input. We conclude that dopaminergic projections from the thalamic subparafascicular nucleus to the inferior colliculus could encode the expected precision of unsigned PEs, attenuating via D2-like receptors the postsynaptic gain of sensory inputs forwarded by the auditory midbrain neurons. This direct dopaminergic modulation of sensory PE signaling has profound implications for both the predictive coding framework and the understanding of dopamine function.

Recognizing reward-related stimuli is crucial for survival. Neuronal projections from the basolateral amygdala (BLA) to the nucleus accumbens (NAc) play an important role in processing reward-related cues. Previous studies revealed synchronization between distant brain regions in reward-sensitive neurocircuits; however, whether the NAc synchronizes with the BLA is unknown. Here, we recorded local field potentials simultaneously from the BLA and NAc of rats during social preference tests and an appetitive conditioning test in which explicit stimuli were associated with food. BLA-NAc coherence in the theta band (5-8 Hz) increased in response to food-associated cues. Meanwhile, the modulatory strength of theta-high gamma (50-110 Hz) phase-amplitude cross-frequency coupling (PAC) in the NAc decreased. Importantly, both of these neuromodulations disappeared upon extinction. In contrast, both theta and gamma power oscillations in each region increased in the presence of social conspecifics or contexts associated with conspecifics, but coherence did not change. To potentially disrupt behavior and associated neural activity, a subgroup of rats was exposed prenatally to valproic acid (VPA), which has been shown to disrupt transcriptome and excitatory/inhibitory balance in the amygdala. VPA-exposed rats demonstrated impulsive-like behavior, but VPA did not affect BLA-NAc coherence. These findings reveal changes in BLA-NAc coherence in response to select reward-related stimuli (i.e., food-predictive cues); the differences between the tasks used here could shed light onto the functional nature of BLA-NAc coherence and are discussed.

Imprinted genes are highly expressed in the hypothalamus; however, whether specific imprinted genes affect hypothalamic neuromodulators and their functions is unknown. It has been suggested that Prader–Willi syndrome (PWS), a neurodevelopmental disorder caused by lack of paternal expression at chromosome 15q11–q13, is characterized by hypothalamic insufficiency. Here, we investigate the role of the paternally expressed Snord116 gene within the context of sleep and metabolic abnormalities of PWS, and we report a significant role of this imprinted gene in the function and organization of the 2 main neuromodulatory systems of the lateral hypothalamus (LH) — namely, the orexin (OX) and melanin concentrating hormone (MCH) — systems. We observed that the dynamics between neuronal discharge in the LH and the sleep-wake states of mice with paternal deletion of Snord116 (PWScr m+/p– ) are compromised. This abnormal state–dependent neuronal activity is paralleled by a significant reduction in OX neurons in the LH of mutant mice. Therefore, we propose that an imbalance between OX- and MCH-expressing neurons in the LH of mutant mice reflects a series of deficits manifested in the PWS, such as dysregulation of rapid eye movement (REM) sleep, food intake, and temperature control.

Listeners differ in their ability to attend to a speech stream in the presence of a competing sound. Differences in speech intelligibility in noise cannot be fully explained by the hearing ability which suggests the involvement of additional cognitive factors. A better understanding of the temporal fluctuations in the ability to pay selective auditory attention to a desired speech stream may help in explaining these variabilities. In order to better understand the temporal dynamics of selective auditory attention, we developed an online auditory attention decoding (AAD) processing pipeline based on speech envelope tracking in the electroencephalogram (EEG). Participants had to attend to one audiobook story while a second one had to be ignored. Online AAD was applied to track the attention toward the target speech signal. Individual temporal attention profiles were computed by combining an established AAD method with an adaptive staircase procedure. The individual decoding performance over time was analyzed and linked to behavioral performance as well as subjective ratings of listening effort, motivation, and fatigue. The grand average attended speaker decoding profile derived in the online experiment indicated performance above chance level. Parameters describing the individual AAD performance in each testing block indicated significant differences in decoding performance over time to be closely related to the behavioral performance in the selective listening task. Further, an exploratory analysis indicated that subjects with poor decoding performance reported higher listening effort and fatigue compared to good performers. Taken together our results show that online EEG based AAD in a complex listening situation is feasible. Adaptive attended speaker decoding profiles over time could be used as an objective measure of behavioral performance and listening effort. The developed online processing pipeline could also serve as a basis for future EEG based near real-time auditory neurofeedback systems.

Cortical injuries (e.g. – strokes or traumatic brain injuries) can create a host of secondary events that further impair the brain’s sensory, motor, or cognitive capabilities. Here, we attempted to isolate the acute effects of the primary injury – the loss of cortical activity – on rodent motor cortex (caudal forelimb area, CFA) without the secondary effects that arise from damage to cortical tissue. We then observed the effects of this loss of activity on the rodent premotor cortex (rostral forelimb area, RFA). In anesthetized rats, CFA was temporarily inactivated with the GABA-A agonist muscimol, disrupting motor network function while leaving neural connectivity intact. Using intracortical microstimulation (ICMS) techniques, we found that CFA inactivation completely abolished ICMS-evoked forelimb movement from RFA yet spared some CFA evoked-movement. Neural recordings confirmed that neural suppression by muscimol was isolated to CFA and did not spread into RFA. We next observed how CFA inactivation suppressed RFA influence on forelimb muscles by obtaining intramuscular electromyographical (EMG) recordings from forelimb muscles during ICMS. EMG recordings showed that despite the presence of evoked movement in CFA, but not RFA, muscle activation in both areas were similarly reduced. These results suggest that the primary reason for the loss of ICMS-evoked movement in RFA is not reduced forelimb muscle activity, but rather a loss of the specific activity between RFA and CFA. Therefore, within the intact motor network of the rat, RFA’s influence on forelimb movement is mediated by CFA, similar to the premotor and motor organization observed in non-human primates.