Journal of Neuroscience

Donders' law, as applied to the arm, predicts that to every location of the hand in space there corresponds a unique posture of the arm as defined by shoulder and elbow angles. This prediction was tested experimentally by asking human subjects to make pointing movements to a select number of target locations starting from a wide range of initial hand locations. The posture of the arm was measured at the start and end of every movement by means of video cameras. It was found that, in general, the posture of the arm at a given hand location does depend on the starting location of the movement and that, consequently, Donders' law is violated in this experimental condition. Kinematic and kinetic factors that could account for the variations in arm posture were investigated. It proved impossible to predict the final posture of the arm purely from kinematics, based on the initial posture of the arm. One hypothesis was successful in predicting final arm postures, namely that the final posture minimizes the amount of work that must be done to transport the arm from the starting location.

Few computational models have addressed the spatiotemporal features of unconstrained three-dimensional (3D) arm motion. Empirical observations made on hand paths, speed profiles, and arm postures during point-to-point movements led to the assumption that hand path and arm posture are independent of movement speed, suggesting that the geometric and temporal properties of movements are decoupled. In this study, we present a computational model of 3D movements for an arm with four degrees of freedom based on the assumption that optimization principles are separately applied at the geometric and temporal levels of control. Geometric properties (path and posture) are defined in terms of geodesic paths with respect to the kinetic energy metric in the Riemannian configuration space. Accordingly, a geodesic path can be generated with less muscular effort than on any other, nongeodesic path, because the sum of all configuration-speed-dependent torques vanishes. The temporal properties of the movement (speed) are determined in task space by minimizing the squared jerk along the selected end-effector path. The integration of both planning levels into a single spatiotemporal representation simplifies the control of arm dynamics along geodesic paths and results in movements with near minimal torque change and minimal peak value of kinetic energy. Thus, the application of Riemannian geometry allows for a reconciliation of computational models previously proposed for the description of arm movements. We suggest that geodesics are an emergent property of the motor system through the exploration of dynamical space. Our data validated the predictions for joint trajectories, hand paths, final postures, speed profiles, and driving torques.

Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as perineuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects.

Twelve normal subjects viewed alternating sequences of unfamiliar faces, unpronounceable nonword letterstrings, and textures while echoplanar functional magnetic resonance images were acquired in seven slices extending from the posterior margin of the splenium to near the occipital pole. These stimuli were chosen to elicit initial category-specific processing in extrastriate cortex while minimizing semantic processing. Overall, faces evoked more activation than did letterstrings. Comparing hemispheres, faces evoked greater activation in the right than the left hemisphere, whereas letterstrings evoked greater activation in the left than the right hemisphere. Faces primarily activated the fusiform gyrus bilaterally, and also activated the right occipitotemporal and inferior occipital sulci and a region of lateral cortex centered in the middle temporal gyrus. Letterstrings primarily activated the left occipitotemporal and inferior occipital sulci. Textures primarily activated portions of the collateral sulcus. In the left hemisphere, 9 of the 12 subjects showed a characteristic pattern in which faces activated a discrete region of the lateral fusiform gyrus, whereas letterstrings activated a nearby region of cortex within the occipitotemporal and inferior occipital sulci. These results suggest that different regions of ventral extrastriate cortex are specialized for processing the perceptual features of faces and letterstrings, and that these regions are intermediate between earlier processing in striate and peristriate cortex, and later lexical, semantic, and associative processing in downstream cortical regions.

The inferior colliculus (IC) is a major auditory structure that integrates synaptic inputs from ascending, descending, and intrinsic sources. Intracellular recordingin situallows direct examination of synaptic inputs to the IC in response to acoustic stimulation. Using this technique and monaural or binaural stimulation, responses in the IC that reflect input from a lower center can be distinguished from responses that reflect synaptic integration within the IC. Our results indicate that many IC neurons receive synaptic inputs from multiple sources. Few, if any, IC neurons acted as simple relay cells. Responses often displayed complex interactions between excitatory and inhibitory sources, such that different synaptic mechanisms could underlie similar response patterns. Thus, it may be an oversimplification to classify the responses of IC neurons as simply excitatory or inhibitory, as is done in many studies. In addition, inhibition and intrinsic membrane properties appeared to play key roles in creatingde novotemporal response patterns in the IC.

The inferior colliculus receives excitatory and inhibitory input from parallel auditory pathways that differ in discharge patterns, latencies, and binaural properties. Processing in the inferior colliculus may depend on the temporal sequence in which excitatory and inhibitory synaptic inputs are activated and on the resulting balance between excitation and inhibition. To explore this issue at the cellular level, we used the novel approach of whole-cell patch-clamp recording in the midbrain of awake bats (Eptesicus fuscus) to record EPSCs or IPSCs. Sound-evoked EPSCs were recorded in most neurons. These EPSCs were frequently preceded by an IPSC, followed by an IPSC, or both. These findings help explain the large latency range and transient responses that characterize inferior colliculus neurons. The EPSC was sometimes followed by long-lasting oscillatory currents, suggesting that a single brief sound sets up a pattern of altered excitability that persists far beyond the duration of the initial sound. In three binaural neurons, ipsilateral sound evoked a large IPSC that partially or totally canceled the EPSC evoked by contralateral sound. In one binaural neuron with ipsilaterally evoked IPSCs, contralaterally evoked IPSCs occurred in response to frequencies above and below the neuron’s best frequency. Thus, both monaural and binaural interactions can occur at single inferior colliculus neurons. These results show that whole-cell patch-clamp recording offers a powerful means of understanding how subthreshold processes determine the responses of auditory neurons.

The precedence effect (PE) describes an illusion produced when two similar sounds are delivered in quick succession (interclick delays of 2–8 msec) from sound sources at different locations so that only a single sound is perceived. The localization of the perceived sound is dominated by the location of the leading sound. If the delays are very short (< 1–2 msec), summing localization occurs and a phantom source is perceived whose location is toward the leading sound. The purpose of these experiments was to look for physiological correlates of the precedence effect and summing localization by recording from single neurons in the inferior colliculus of the anesthetized cat. Click stimuli were delivered under two different situations: over headphones in dichotic experiments and through two speakers in an anechoic room in free-field studies. In the latter case the cat was placed midway between the speakers and a single click stimulus was delivered to each speaker with variable interclick delays (ICDs). Most cells, under both dichotic and free-field conditions, exhibited a form of the precedence effect in which the response to the lagging click was suppressed when ICDs were short. The suppression of the lagging click, or echo, was measured by recovery curves, which plotted the response of the lagging click as a function of ICD. There was considerable variability in the recovery curves from different cells: the ICDs at which the recovery reached 50%, which is a measure of the echo threshold for the cell, ranged from 1 to 100 msec with a median of 20 msec. Human psychophysical experiments report echo thresholds for clicks ranging from 2 to 8 msec. If we assume that absolute echo threshold is determined by the cells with shortest recovery curves, then the thresholds for single cells are in accord with the psychophysical results. The possible sites of generation of the echo suppression are also considered. Changes in the relative level of the leading and lagging clicks produced the expected shifts in the recovery curves. With short ICDs in the summing localization range (between about +/- 2 msec) cells also showed responses consonant with the human psychophysical result that the sound source is localized to a phantom image between the two speakers and toward the leading one. The location of the image varied systematically with the relative levels or ICDs of the clicks.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study we have investigated the processing of auditory cues for sound localization in the great horned owl (Bubo virginianus). Previous studies have shown that the barn owl, whose ears are asymmetrically oriented in the vertical plane, has a 2-dimensional, topographic representation of auditory space in the external division of the inferior colliculus (ICx). As in the barn owl, the great horned owl's ICx is anatomically distinct and projects to the optic tectum. Neurons in ICx respond over only a small range of azimuths (mean = 32 degrees), and azimuth is topographically mapped. In contrast to the barn owl, the great horned owl has bilaterally symmetrical ears and its receptive fields are not restricted in elevation. The binaural cues available for sound localization were measured both with cochlear microphonic recordings and with a microphone attached to a probe tube in the auditory canal. Interaural time disparity (ITD) varied monotonically with azimuth. Interaural intensity differences (IID) also changed with azimuth, but the largest IIDs were less than 15 dB, and the variation was not monotonic. Neither ITD nor IID varied systematically with changes in the vertical position of a sound source. We used dichotic stimulation to determine the sensitivity of ICx neurons to these binaural cues. Best ITD of ICx units was topographically mapped and strongly correlated with receptive-field azimuth. The width of ITD tuning curves, measured at 50% of the maximum response, averaged 72 microseconds. All ICx neurons responded only to binaural stimulation and had nonmonotonic IID tuning curves. Best IID was weakly, but significantly, correlated with best ITD (r = 0.39, p less than 0.05). The IID tuning curves, however, were broad (mean 50% width = 24 dB), and 67% of the units had best IIDs within 5 dB of 0 dB IID. ITD tuning was sensitive to variations in IID in the direction opposite to that expected for time-intensity trading, but the magnitude of this effect was only 1.5 microseconds/dB IID. We conclude that, in the great horned owl, the spatial selectivity of ICx neurons arises primarily from their ITD tuning. Except for the absence of elevation selectivity and the narrow range of best IIDs, ICx in the great horned owl appears to be organized much the same as in the barn owl.

An essential component of goal-directed decision-making is the ability to maintain flexible responding based on the value of a given reward, or “reinforcer.” The medial orbitofrontal cortex (mOFC), a subregion of the ventromedial prefrontal cortex, is uniquely positioned to regulate this process. We trained mice to nose poke for food reinforcers and then stimulated this region using CaMKII-driven G_s-coupled designer receptors exclusively activated by designer drugs (DREADDs). In other mice, we silenced the neuroplasticity-associated neurotrophin brain-derived neurotrophic factor (BDNF). Activation of G_s-DREADDs increased behavioral sensitivity to reinforcer devaluation, whereasBdnfknockdown blocked sensitivity. These changes were accompanied by modifications in breakpoint ratios in a progressive ratio task, and they were recapitulated inBdnf^+/−mice. Replacement of BDNF selectively in the mOFC inBdnf^+/−mice rescued behavioral deficiencies, as well as phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2). Thus, BDNF expression in the mOFC is both necessary and sufficient for the expression of typical effort allocation relative to an anticipated reinforcer. Additional experiments indicated that expression of the immediate-early gene c-foswas aberrantly elevated in theBdnf^+/−dorsal striatum, and BDNF replacement in the mOFC normalized expression. Also, systemic administration of an MAP kinase kinase inhibitor increased breakpoint ratios, whereas the addition of discrete cues bridging the response–outcome contingency rescued breakpoints inBdnf^+/−mice. We argue that BDNF–ERK1/2 in the mOFC is a key regulator of “online” goal-directed action selection.

SIGNIFICANCE STATEMENTGoal-directed response selection often involves predicting the consequences of one's actions and the value of potential payoffs. Lesions or chemogenetic inactivation of the medial orbitofrontal cortex (mOFC) in rats induces failures in retrieving outcome identity memories (Bradfield et al., 2015), suggesting that the healthy mOFC serves to access outcome value information when it is not immediately observable and thereby guide goal-directed decision-making. Our findings suggest that the mOFC also bidirectionally regulates effort allocation for a given reward and that expression of the neurotrophin BDNF in the mOFC is both necessary and sufficient for mice to sustain stable representations of reinforcer value.

Some rats [sign-trackers (STs)] are especially prone to attribute incentive salience to reward cues, relative to others [goal-trackers (GTs)]. Thus, reward cues are more likely to promote maladaptive reward-seeking behavior in STs than GTs. Here, we asked whether STs and GTs differ on another trait that can contribute to poor restraint over behavior evoked by reward cues. We report that, relative to GTs, STs have poor control over attentional performance, due in part to insufficient cholinergic stimulation of cortical circuitry. We found that, relative to GTs, STs showed poor performance on a sustained attention task (SAT). Furthermore, their performance fluctuated rapidly between periods of good to near-chance performance. This finding was reproduced using a separate cohort of rats. As demonstrated earlier, performance on the SAT was associated with increases in extracellular levels of cortical acetylcholine (ACh); however, SAT performance-associated increases in ACh levels were significantly attenuated in STs relative to GTs. Consistent with the view that the modulatory effects of ACh involve stimulation of α4β2* nicotinic ACh receptors (nAChRs), systemic administration of the partial nAChR agonist ABT-089 improved SAT performance in STs and abolished the difference between SAT-associated ACh levels in STs and GTs. Neither the nonselective nAChR agonist nicotine nor the psychostimulant amphetamine improved SAT performance. These findings suggest that individuals who have a propensity to attribute high-incentive salience to reward cues also exhibit relatively poor attentional control. A combination of these traits may render individuals especially vulnerable to disorders, such as obesity and addiction.