In many preclinical spinal cord injury (SCI) studies, assessment of locomotion recovery is key to understanding the effectiveness of the experimental intervention. In such rat SCI studies, the most basic locomotor recovery scoring system is a subjective observation of animals freely roaming in an open field, the Basso Beattie Bresnahan (BBB) score. In comparison, CatWalk is an automated gait analysis system, providing further parameter specifications. Although together the CatWalk parameters encompass gait, studies consistently report single parameters, which differ in significance from other behavioral assessments. Therefore, we believe no single parameter produced by the CatWalk can represent the fully-coordinated motion of gait. Typically, other locomotor assessments, such as the BBB score, combine several locomotor characteristics into a representative score. For this reason, we ranked the most distinctive CatWalk parameters between uninjured and SC injured rats. Subsequently, we combined nine of the t...

The basal ganglia have long been considered crucial for associative learning, but whether they also are involved in another type of learning, error-based motor learning, is not clear. Error-based learning has been considered the province of the cerebellum. However, learning to use a robotic arm and saccade adaptation, which use error-based learning, are facilitated by motivation, which is a function of the basal ganglia. Additionally, patients with Parkinson’s disease, a basal ganglia deficit, show slower saccade adaptation than age matched controls. To further investigate whether the basal ganglia actually influence error-based learning, we reversibly inactivated the oculomotor portion of the substantia nigra pars reticulata (SNr) in two monkeys and tested saccade adaptation. Here, we show that nigral inactivation affected saccade adaptation. In particular, the inactivation facilitated the amplitude decrease adaptation of ipsiversive saccades. Consistent with previous studies, no effect was seen on the am...

Stomatin-like protein-3 (STOML3) is an integral membrane protein expressed in the cilia of olfactory sensory neurons (OSNs), but its functional role in this cell type has never been addressed. STOML3 is also expressed in dorsal root ganglia neurons, where it has been shown to be required for normal touch sensation. Here, we extended previous results indicating that STOML3 is mainly expressed in the knob and proximal cilia of OSNs. We additionally showed that mice lacking STOML3 have a morphologically normal olfactory epithelium. Because of its presence in the cilia, together with known olfactory transduction components, we hypothesized that STOML3 could be involved in modulating odorant responses in OSNs. To investigate the functional role of STOML3, we performed loose patch recordings from wild-type (WT) and Stoml3 knock-out (KO) OSNs. We found that spontaneous mean firing activity was lower with additional shift in interspike intervals (ISIs) distributions in Stoml3 KOs compared with WT neurons. Moreover...

Impairments of working memory (WM) are commonly observed in a variety of neurodegenerative disorders but they are difficult to quantitatively assess in clinical cases. Recent studies in experimental animals have used low-dose ketamine (an NMDA receptor antagonist) to disrupt WM, partly mimicking the pathophysiology of schizophrenia. Here, we developed a novel behavioral paradigm to assess multiple components of WM and applied it to monkeys with and without ketamine administration. In an oculomotor foraging task, the animals were presented with 15 identical objects on the screen. One of the objects was associated with a liquid reward, and monkeys were trained to search for the target by generating sequential saccades under a time constraint. We assumed that the occurrence of recursive movements to the same object might reflect WM dysfunction. We constructed a “foraging model” that incorporated (1) memory capacity, (2) memory decay, and (3) utility rate; this model was able to explain more than 92% of the va...

GABAergic projections neurons of the substantia nigra reticulata (SNr), through an extensive network of dendritic arbors and axon collaterals, provide robust inhibitory input to neighboring dopaminergic neurons in the substantia nigra compacta (SNc). Angiotensin-II (Ang-II) receptor signaling increases SNc dopaminergic neuronal sensitivity to insult, thus rendering these cells susceptible to dysfunction and destruction. However, the mechanisms by which Ang-II regulates SNc dopaminergic neuronal activity are unclear. Given the complex relationship between SN dopaminergic and GABAergic neurons, we hypothesized that Ang-II could regulate SNc dopaminergic neuronal activity directly and indirectly by modulating SNr GABAergic neurotransmission. Here, using transgenic mice, slice electrophysiology, and optogenetics, we provide evidence of an AT1 receptor-mediated signaling mechanism in SNr GABAergic neurons where Ang-II suppresses electrically-evoked neuronal output by facilitating postsynaptic GABAA receptors (G...

Microtubules (MTs) are cytoskeletal elements that provide structural support and act as roadways for intracellular transport in cells. MTs are also needed for neurons to extend and maintain long axons and dendrites that establish connectivity to transmit information through the nervous system. Therefore, in neurons, the ability to independently regulate cytoskeletal stability and MT-based transport in different cellular compartments is essential. Posttranslational modification of MTs is one mechanism by which neurons regulate the cytoskeleton. The carboxypeptidase CCP1 negatively regulates posttranslational polyglutamylation of MTs. In mammals, loss of CCP1, and the resulting hyperglutamylation of MTs, causes neurodegeneration. It has also long been known that CCP1 expression is activated by neuronal injury; however, whether CCP1 plays a neuroprotective role after injury is unknown. Using shRNA-mediated knock-down of CCP1 in embryonic rat spinal cord cultures, we demonstrate that CCP1 protects spinal cord ...

Persistent firing is believed to be a cellular correlate of working memory. While the effects of noradrenaline (NA) on working memory have widely been described, its effect on the cellular mechanisms of persistent firing remains largely unknown. Using in vitro intracellular recordings, we demonstrate that persistent firing is supported by individual neurons in hippocampal CA1 pyramidal cells through cholinergic receptor activation, but is dramatically attenuated by NA. In contrast to the classical theory that recurrent synaptic excitation supports persistent firing, suppression of persistent firing by NA was independent of synaptic transmission, indicating that the mechanism is intrinsic to individual cells. In agreement with detrimental effects of cAMP on working memory, we demonstrate that the suppressive effect of NA was through cAMP-PKA pathway. In addition, activation of β1 and/or β3 adrenergic receptors, which increases cAMP levels, suppressed persistent firing. These results are in line with working...

Grand neuroscience projects, such as connectomics, have a recurrent tendency to overpromise and underdeliver. Here I critically assess what is done in contrast with what is claimed about such endeavors, especially when the results are “horizontal” and the conclusions “vertical”, namely, when maps of one level (synaptic connections) are conflated with mappings between levels (neural function, animal behavior, cognitive processes). I argue that to suggest that connectomics will give us the mind of a mouse, a human or even a fly is conceptually flawed. Even if we, neuroscientists, do not take our metaphors literally, we should take them seriously. Imagine that a group of prominent psychologists wrote a paper about the brain of a mouse disregarding neural matters. Measuring attention or perception at unprecedented resolution, these scientists would promise to solve the mouse’s brain (by decree, it would emerge from “mind stuff”). Published in a top cognitive science journal, “The Brain of a Mouse” would inspi...

We previously argued that the neuroscience community has a role in environmental conservation because protection of biodiversity and the specialized behavioral adaptions of animals is essential to understanding brain structure and function. Preserving biodiversity and the natural world is also linked to human mental health and broadens our insight on the origins of psychiatric disorders like stress, anxiety, and depression. The study of neuroscience has become a global scientific pursuit that involves thousands of researchers and has an economic impact in the billions of dollars. As a group of biomedical research scientists, neuroscientists have the knowledge base and public credibility to convincingly promote sustainable environmental actions and policies. Here, we outline several key areas in which we as a neuroscience academic community can participate to preserve a rich global biodiversity and confront the environmental crises that lie before us.

What role does color play in the neural representation of complex shapes? We approached the question by measuring color responses of face-selective neurons, using fMRI-guided microelectrode recording of the middle and anterior face patches of inferior temporal cortex (IT) in rhesus macaques. Face-selective cells responded weakly to pure color (equiluminant) photographs of faces. But many of the cells nonetheless showed a bias for warm colors when assessed using images that preserved the luminance contrast relationships of the original photographs. This bias was also found for non-face-selective neurons. Fourier analysis uncovered two components: the first harmonic, accounting for most of the tuning, was biased toward reddish colors, corresponding to the L>M pole of the L-M cardinal axis. The second harmonic showed a bias for modulation between blue and yellow colors axis, corresponding to the S-cone axis. To test what role face-selective cells play in behavior, we related the information content of the neu...