RESUMEN
Neuroscience curricula vary widely across higher education institutions due to the lack of an accrediting body or a set of unified educational concepts or outcomes. Each institution has developed a unique set of fundamental knowledge, topical subdisciplines, and core competencies to be delivered in a neuroscience program. Core concepts would provide neuroscience departments and programs with a generally agreed upon set of overarching principles that organize knowledge and can be applied to all sub-disciplines of the field, providing a useful framework from which to approach neuroscience education. We set out to develop a consensus set of neuroscience core concepts to aid in higher education curricular development and assessment. Suggestions for neuroscience core concepts were solicited from neuroscience faculty in a nationwide survey and analyzed using an inductive, independent coding model to identify eight core concepts based upon survey responses. Accompanying explanatory paragraphs for each core concept were developed through an iterative process. We presented the resulting core concepts to 134 neuroscience educators at a satellite session of the Faculty for Undergraduate Neuroscience 2020 Summer Virtual Meeting (SVM). Individuals and groups of faculty provided feedback regarding the accuracy, comprehensiveness, and clarity of each concept and explanatory paragraph, as well as the structure of the document as a whole. We continue to refine the core concepts based upon this feedback and will distribute the final document in a subsequent publication. Following publication of the finalized list of core concepts, we will develop tools to help educators incorporate the core concepts into their curricula.
RESUMEN
Sensory feedback is critical for normal locomotion and adaptation to external perturbations during movement. Feedback provided by group Ia afferents influences motor output both directly through monosynaptic connections and indirectly through spinal interneuronal circuits. For example, the circuit responsible for reciprocal inhibition, which acts to prevent co-contraction of antagonist flexor and extensor muscles, is driven by Ia afferent feedback. Additionally, circuits mediating presynaptic inhibition can limit Ia afferent synaptic transmission onto central neuronal targets in a task-specific manner. These circuits can also be activated by stimulation of proprioceptive afferents. Rodent locomotion rapidly matures during postnatal development; therefore, we assayed the functional status of reciprocal and presynaptic inhibitory circuits of mice at birth and compared responses with observations made after 1 wk of postnatal development. Using extracellular physiological techniques from isolated and hemisected spinal cord preparations, we demonstrate that Ia afferent-evoked reciprocal inhibition is as effective at blocking antagonist motor neuron activation at birth as at 1 wk postnatally. In contrast, at birth conditioning stimulation of muscle nerve afferents failed to evoke presynaptic inhibition sufficient to block functional transmission at synapses between Ia afferents and motor neurons, even though dorsal root potentials could be evoked by stimulating the neighboring dorsal root. Presynaptic inhibition at this synapse was readily observed, however, at the end of the first postnatal week. These results indicate Ia afferent feedback from the periphery to central spinal circuits is only weakly gated at birth, which may provide enhanced sensitivity to peripheral feedback during early postnatal experiences.
Asunto(s)
Neuronas GABAérgicas/fisiología , Inhibición Neural , Propiocepción/fisiología , Células Receptoras Sensoriales/fisiología , Médula Espinal/fisiología , Transmisión Sináptica , Potenciales de Acción , Animales , Retroalimentación Sensorial , Ratones , Ratones Endogámicos C57BL , Neuronas Motoras/fisiología , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/fisiología , Médula Espinal/crecimiento & desarrollo , Raíces Nerviosas Espinales/crecimiento & desarrollo , Raíces Nerviosas Espinales/fisiologíaRESUMEN
Core concepts provide a framework for organizing facts and understanding in neuroscience higher education curricula. Core concepts are overarching principles that identify patterns in neuroscience processes and phenomena and can be used as a foundational scaffold for neuroscience knowledge. The need for community-derived core concepts is pressing, because both the pace of research and number of neuroscience programs are rapidly expanding. While general biology and many subdisciplines within biology have identified core concepts, neuroscience has yet to establish a community-derived set of core concepts for neuroscience higher education. We used an empirical approach involving more than 100 neuroscience educators to identify a list of core concepts. The process of identifying neuroscience core concepts was modeled after the process used to develop physiology core concepts and involved a nationwide survey and a working session of 103 neuroscience educators. The iterative process identified eight core concepts and accompanying explanatory paragraphs. The eight core concepts are abbreviated as communication modalities, emergence, evolution, gene-environment interactions, information processing, nervous system functions, plasticity, and structure-function. Here, we describe the pedagogical research process used to establish core concepts for the neuroscience field and provide examples on how the core concepts can be embedded in neuroscience education.
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Cognición , Estudiantes , Humanos , Comunicación , Curriculum , ConocimientoRESUMEN
Commissural inhibitory interneurons (INs) are integral components of the locomotor circuitry that coordinate left-right motor activity during movements. We have shown that GABA-mediated synaptic transmission plays a key role in generating alternating locomotor-like activity in the mouse spinal cord (Hinckley et al., 2005a). The primary objective of our study was to determine whether properties of lamina VIII (LVIII) GABAergic INs in the spinal cord of GAD67::GFP transgenic mice fit the classification of rhythm-coordinating neurons in the locomotor circuitry. The relatively large green fluorescent protein-expressing (GFP(+)) INs had comparable morphological and electrophysiological properties, suggesting that they comprised a homogenous neuronal population. They displayed multipolar and complex dendritic arbors in ipsilateral LVII-LVIII, and their axonal projections crossed the ventral commissure and branched into contralateral ventral, medial, and dorsal laminae. Putative synaptic contacts evident as bouton-like varicosities were detected in close apposition to lateral motoneurons, Renshaw cells, other GFP(+) INs, and unidentified neurons. Exposure to a rhythmogenic mixture triggered locomotor-like rhythmic firing in the majority of LVIII GFP(+) INs. Their induced oscillatory activity was out-of-phase with bursts of contralateral motoneurons and in-phase with bouts of ipsilateral motor activity. Membrane voltage oscillations were elicited by rhythmic increases in excitatory synaptic drive and might have been augmented by three types of voltage-activated cationic currents known to increase neuronal excitability. Based on their axonal projections and activity pattern, we propose that this population of GABAergic INs forms a class of local commissural inhibitory interneurons that are integral component of the locomotor circuitry.
Asunto(s)
Interneuronas/fisiología , Actividad Motora/fisiología , Neuronas Motoras/fisiología , Red Nerviosa/fisiología , Médula Espinal/fisiología , Ácido gamma-Aminobutírico/fisiología , Potenciales de Acción/fisiología , Animales , Animales Recién Nacidos , Femenino , Glutamato Descarboxilasa/fisiología , Interneuronas/citología , Interneuronas/enzimología , Masculino , Ratones , Ratones Transgénicos , Neuronas Motoras/citología , Neuronas Motoras/enzimología , Red Nerviosa/citología , Red Nerviosa/enzimología , Médula Espinal/citología , Médula Espinal/enzimologíaRESUMEN
Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na(+) spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.
Asunto(s)
Potenciales de Acción/fisiología , Hipertensión/fisiopatología , Neuronas/fisiología , Núcleo Hipotalámico Paraventricular/fisiopatología , Condicionamiento Físico Animal/fisiología , Núcleo Solitario/fisiopatología , Animales , Masculino , Plasticidad Neuronal/fisiología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKYRESUMEN
Accumulating evidence supports a contribution of the hypothalamic paraventricular nucleus (PVN) to sympathoexcitation and elevated blood pressure in renovascular hypertension. However, the underlying mechanisms resulting in altered neuronal function in hypertensive rats remain largely unknown. Here, we aimed to address whether the transient outward potassium current (I(A)) in identified rostral ventrolateral medulla (RVLM)-projecting PVN neurones is altered in hypertensive rats, and whether such changes affected single and repetitive action potential properties and associated changes in intracellular Ca(2+) levels. Patch-clamp recordings obtained from PVN-RVLM neurons showed a reduction in I(A) current magnitude and single channel conductance, and an enhanced steady-state current inactivation in hypertensive rats. Morphometric reconstructions of intracellularly labelled PVN-RVLM neurons showed a diminished dendritic surface area in hypertensive rats. Consistent with a diminished I(A) availability, action potentials in PVN-RVLM neurons in hypertensive rats were broader, decayed more slowly, and were less sensitive to the K(+) channel blocker 4-aminopyridine. Simultaneous patch clamp recordings and confocal Ca(2+) imaging demonstrated enhanced action potential-evoked intracellular Ca(2+) transients in hypertensive rats. Finally, spike broadening during repetitive firing discharge was enhanced in PVN-RVLM neurons from hypertensive rats. Altogether, our results indicate that diminished I(A) availability constitutes a contributing mechanism underlying aberrant central neuronal function in renovascular hypertension.
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Potenciales de Acción , Hipertensión Renovascular/fisiopatología , Bulbo Raquídeo/fisiopatología , Núcleo Hipotalámico Paraventricular/fisiopatología , Potasio/metabolismo , Terminales Presinápticos , Sistema Nervioso Simpático/fisiopatología , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas WistarRESUMEN
Reciprocal inhibition of motor neurons via Ia inhibitory interneurons recruited by stimulation of proprioceptive afferents supplying antagonist muscles has been well described. Changes in the efficacy of inhibition, and sometimes even a switch from inhibition to facilitation, have been reported in the literature after disruption of descending pathways. We sought to test whether such facilitation could be expressed in normal animals by evaluating the presence of facilitation in acute preparations from uninjured animals. Using an isolated spinal cord preparation from neonatal mice, changes in the monosynaptic stretch reflex response in knee flexor motor neurons (posterior biceps semitendinosus; PBST) were monitored following conditioning stimulation of proprioceptive sensory afferents in other muscle nerves. As expected for reciprocal inhibition, conditioning by stimulation of quadriceps (knee extensors and PBST antagonists) sensory afferents resulted in inhibition of the stretch reflex response. Facilitation, however, of the stretch reflex response by quadriceps conditioning stimulation was observed when the glycinergic reciprocal inhibitory pathway was blocked by application of strychnine. Facilitation was elicited by low-threshold proprioceptive afferents and occurred at latencies consistent with a disynaptic circuit. The magnitude of facilitation was larger at birth than at one week postnatal. Our results also suggest reciprocal facilitation is restricted to antagonist muscle pairs, as facilitation of PBST responses was not observed when conditioned with the obturator nerve supplying the adductor muscles. Overall, these data suggest the efficacy of facilitation is modulated during the first postnatal week, while the specificity of facilitation is already established by birth.
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Neuronas Motoras/fisiología , Neuronas Aferentes/fisiología , Propiocepción/fisiología , Médula Espinal/fisiología , Vías Aferentes/crecimiento & desarrollo , Vías Aferentes/fisiología , Animales , Animales Recién Nacidos , Ratones Endogámicos C57BL , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Inhibición Neural , Reflejo de Estiramiento , Médula Espinal/crecimiento & desarrolloRESUMEN
C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a "signaling ensemble") for cholinergic regulation of outward K(+) currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges for understanding the role of C-bouton regulation and dysregulation in human health and disease. The development of new therapeutic interventions for devastating neurological conditions will rely on a complete understanding of the molecular mechanisms that underlie these complex synapses. Therefore, to close this review, we propose a comprehensive hypothetical mechanism for the cholinergic modification of α-MN excitability at C-bouton synapses, based on findings in several well-characterized neuronal systems.
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Neuronas Motoras/fisiología , Terminales Presinápticos/fisiología , Médula Espinal/citología , Natación/fisiología , Sinapsis/fisiología , Proteínas de Transporte Vesicular de Acetilcolina/metabolismo , Animales , Señalización del Calcio , Humanos , Red Nerviosa/fisiología , Receptor Muscarínico M2 , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Sinapsis/genética , Proteínas de Transporte Vesicular de Acetilcolina/genéticaRESUMEN
Neurohumoral activation, a hallmark in heart failure (HF), is linked to the progression and mortality of HF patients. Thus, elucidating its precise underlying mechanisms is of critical importance. Other than its classic peripheral vasodilatory actions, the gas NO is a pivotal neurotransmitter in the central nervous system control of the circulation. While accumulating evidence supports a contribution of blunted NO function to neurohumoral activation in HF, the precise cellular sources, and NO synthase (NOS) isoforms involved, remain unknown. Here, we used a multidisciplinary approach to study the expression, cellular distribution, and functional relevance of the endothelial NOS isoform within the hypothalamic paraventricular nucleus in sham and HF rats. Our results show high expression of endothelial NOS in the paraventricular nucleus (mostly confined to astroglial cells), which contributes to constitutive NO bioavailability, as well as tonic inhibition of presympathetic neuronal activity and sympathoexcitatory outflow from the paraventricular nucleus. A diminished endothelial NOS expression and endothelial NOS-derived NO availability were found in the paraventricular nucleus of HF rats, resulting, in turn, in blunted NO inhibitory actions on neuronal activity and sympathoexcitatory outflow. Taken together, our study supports blunted central nervous system endothelial NOS-derived NO as a pathophysiological mechanism underlying neurohumoral activation in HF.
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Sistema Nervioso Central/enzimología , Insuficiencia Cardíaca/metabolismo , Neurotransmisores/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Animales , Astrocitos/enzimología , Astrocitos/metabolismo , Sistema Nervioso Central/metabolismo , Ecocardiografía , Técnicas de Silenciamiento del Gen , Corazón/fisiopatología , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/genética , Hemodinámica , Inmunohistoquímica , Masculino , Bulbo Raquídeo/enzimología , Bulbo Raquídeo/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Confocal , Neuronas/metabolismo , Neurotransmisores/genética , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Oligonucleótidos Antisentido/genética , Núcleo Hipotalámico Paraventricular/enzimología , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas WistarRESUMEN
Despite the fact that paraventricular nucleus (PVN) neurones innervating the rostral ventrolateral medulla (RVLM) play important roles in the control of sympathetic function both in physiological and pathological conditions, the precise mechanisms controlling their activity are still incompletely understood. In the present study, we evaluated whether the transient outward potassium current I(A) is expressed in PVN-RVLM neurones, characterized its biophysical and pharmacological properties, and determined its role in shaping action potentials and firing discharge in these neurones. Patch-clamp recordings obtained from retrogradely labelled, PVN-RVLM neurones indicate that a 4-AP sensitive, TEA insensitive current, with biophysical properties consistent with I(A), is present in these neurones. Pharmacological blockade of I(A) depolarized resting V(m) and prolonged Na(+) action potential duration, by increasing its width and by slowing down its decay time course. Interestingly, blockade of I(A) either increased or decreased the firing activity of PVN-RVLM neurones, supporting the presence of subsets of PVN-RVLM neurones differentially modulated by I(A). In all cases, the effects of I(A) on firing activity were prevented by a broad spectrum Ca(2+) channel blocker. Immunohistochemical studies suggest that I(A) in PVN-RVLM neurons is mediated by Kv1.4 and/or Kv4.3 channel subunits. Overall, our results demonstrate the presence of I(A) in PVN-RVLM neurones, which actively modulates their action potential waveform and firing activity. These studies support I(A) as an important intrinsic mechanism controlling neuronal excitability in this central presympathetic neuronal population.