Tomoko Yamagata

Transformation of a Virtual Action Plan into a Motor Plan in the Premotor Cortex

Before preparing to initiate a forthcoming motion, we often acquire information about the future action without specifying actual motor parameters. The information for planning an action at this conceptual level can be provided with verbal commands or nonverbal signals even before the associated motor targets are visible. Under these conditions, the information signifying a virtual action plan must be transformed to information that can be used for constructing a motor plan to initiate specific movements. To determine whether the premotor cortex is involved in this process, we examined neuronal activity in the dorsal premotor cortex (PMd) of monkeys performing a behavioral task designed to isolate the behavioral stages of the acquisition of information for a future action and the construction of a motor plan. We trained the animals to receive a symbolic instruction (color and shape of an instruction cue) to determine whether to select the right or left of targets to reach, despite the physical absence of targets. Subsequently, two targets appeared on a screen at different locations. The animals then determined the correct target (left or right) based on the previous instruction and prepared to initiate a reaching movement to an actual target. The experimental design dissociated the selection of the right/left at an abstract level (action plan) from the physical motor plan. Here, we show that activity of individual PMd neurons initially reflects a virtual action plan transcending motor specifics, before these neurons contribute to a transformation process that leads to activity encoding a motor plan.

Distinct Information Representation and Processing for Goal-Directed Behavior in the Dorsolateral and Ventrolateral Prefrontal Cortex and the Dorsal Premotor Cortex

Although the lateral prefrontal cortex (lPFC) and dorsal premotor cortex (PMd) are thought to be involved in goal-directed behavior, the specific roles of each area still remain elusive. To characterize and compare neuronal activity in two sectors of the lPFC [dorsal (dlPFC) and ventral (vlPFC)] and the PMd, we designed a behavioral task for monkeys to explore the differences in their participation in four aspects of information processing: encoding of visual signals, behavioral goal retrieval, action specification, and maintenance of relevant information. We initially presented a visual object (an instruction cue) to instruct a behavioral goal (reaching to the right or left of potential targets). After a subsequent delay, a choice cue appeared at various locations on a screen, and the animals could specify an action to achieve the behavioral goal. We found that vlPFC neurons amply encoded object features of the instruction cues for behavioral goal retrieval and, subsequently, spatial locations of the choice cues for specifying the actions. By contrast, dlPFC and PMd neurons rarely encoded the object features, although they reflected the behavioral goals throughout the delay period. After the appearance of the choice cues, the PMd held information for action throughout the specification and preparation of reaching movements. Remarkably, lPFC neurons represented information for the behavioral goal continuously, even after the action specification as well as during its execution. These results indicate that area-specific representation and information processing at progressive stages of the perception–action transformation in these areas underlie goal-directed behavior.

Processing of Visual Signals for Direct Specification of Motor Targets and for Conceptual Representation of Action Targets in the Dorsal and Ventral Premotor Cortex

Previous reports have indicated that the premotor cortex (PM) uses visual information for either direct guidance of limb movements or indirect specification of action targets at a conceptual level. We explored how visual inputs signaling these two different categories of information are processed by PM neurons. Monkeys performed a delayed reaching task after receiving two different sets of visual instructions, one directly specifying the spatial location of a motor target (a direct spatial-target cue) and the other providing abstract information about the spatial location of a motor target by indicating whether to select the right or left target at a conceptual level (a symbolic action-selection cue). By comparing visual responses of PM neurons to the two sets of visual cues, we found that the conceptual action plan indicated by the symbolic action-selection cue was represented predominantly in dorsal PM (PMd) neurons with a longer latency (150 ms), whereas both PMd and ventral PM (PMv) neurons responded with a shorter latency (90 ms) when the motor target was directly specified with the direct spatial-target cue. We also found that excited, but not inhibited, responses of PM neurons to the direct spatial-target cue were biased toward contralateral preference. In contrast, responses to the symbolic action-selection cue were either excited or inhibited without laterality preference. Taken together, these results suggest that the PM constitutes a pair of distinct circuits for visually guided motor act; one circuit, linked more strongly with PMd, carries information for retrieving action instruction associated with a symbolic cue, and the other circuit, linked with PMd and PMv, carries information for directly specifying a visuospatial position of a reach target.

Involvement of the globus pallidus in behavioral goal determination and action specification.

Multiple loop circuits interconnect the basal ganglia and the frontal cortex, and each part of the cortico-basal ganglia loops plays an essential role in neuronal computational processes underlying motor behavior. To gain deeper insight into specific functions played by each component of the loops, we compared response properties of neurons in the globus pallidus (GP) with those in the dorsal premotor cortex (PMd) and the ventrolateral and dorsolateral prefrontal cortex (vlPFC and dlPFC) while monkeys performed a behavioral task designed to include separate processes for behavioral goal determination and action selection. Initially, visual signals instructed an abstract behavioral goal, and seconds later, a choice cue to select an action was presented. When the instruction cue appeared, GP neurons started to reflect visual features as early as vlPFC neurons. Subsequently, GP neurons began to reflect goals informed by the visual signals no later than neurons in the PMd, vlPFC, and dlPFC, indicating that the GP is involved in the early determination of behavioral goals. In contrast, action specification occurred later in the GP than in the cortical areas, and the GP was not as involved in the process by which a behavioral goal was transformed into an action. Furthermore, the length of time representing behavioral goal and action was shorter in the GP than in the PMd and dlPFC, indicating that the GP may play an important role in detecting individual behavioral events. These observations elucidate the involvement of the GP in goal-directed behavior.

Odorant Concentration Differentiator for Intermittent Olfactory Signals

Animals need to discriminate differences in spatiotemporally distributed sensory signals in terms of quality as well as quantity for generating adaptive behavior. Olfactory signals characterized by odor identity and concentration are intermittently distributed in the environment. From these intervals of stimulation, animals process odorant concentration to localize partners or food sources. Although concentration–response characteristics in olfactory neurons have traditionally been investigated using single stimulus pulses, their behavior under intermittent stimulus regimens remains largely elusive. Using the silkmoth (Bombyx mori) pheromone processing system, a simple and behaviorally well-defined model for olfaction, we investigated the neuronal representation of odorant concentration upon intermittent stimulation in the naturally occurring range. To the first stimulus in a series, the responses of antennal lobe (AL) projection neurons (PNs) showed a concentration dependence as previously shown in many olfactory systems. However, PN response amplitudes dynamically changed upon exposure to intermittent stimuli of the same odorant concentration and settled to a constant, largely concentration-independent level. As a result, PN responses emphasized odorant concentration changes rather than encoding absolute concentration in pulse trains of stimuli. Olfactory receptor neurons did not contribute to this response transformation which was due to long-lasting inhibition affecting PNs in the AL. Simulations confirmed that inhibition also provides advantages when stimuli have naturalistic properties. The primary olfactory center thus functions as an odorant concentration differentiator to efficiently detect concentration changes, thereby improving odorant source orientation over a wide concentration range.

GFP Labeling of Neurosecretory Cells with the GAL4/UAS System in the Silkmoth Brain Enables Selective Intracellular Staining of Neurons

Abstract The microbrain of the silkmoth, Bombyx mori, is a model system for analyzing the neural mechanisms underlying stimulus-driven behavior, and numerous studies using physiological and morphological methods have accumulated. However, one of the limitations of this system is a lack of methodology for labeling specific subsets of neurons. Targeted gene expression with the GAL4/UAS system, which was recently developed, may overcome this disadvantage. To test the GAL4/UAS system in the silkmoth brain, we generated two GAL4 driver lines in which GAL4 expression was under the control of either the bombyxin or prothoracicotropic hormone (PTTH) promoter. Crosses of moths from these lines with a UAS-GFP line showed that green fluorescent protein (GFP) was exclusively expressed in bombyxin or PTTH neurosecretory brain cells. Using these lines, we developed a visually guided method to selectively insert an electrode into and intracellulary stain GFP-expressing cells using fluorescence as a landmark. This work provides a novel method to visualize specific subsets of neurons in the silkmoth brain and to observe detailed structures in a single identified neuron from different individuals.

Rostrocaudal functional gradient among the pre-dorsal premotor cortex, dorsal premotor cortex and primary motor cortex in goal-directed motor behaviour

The dorsal premotor cortex residing in the dorsolateral aspect of area 6 is a rostrocaudally elongated area that is rostral to the primary motor cortex (M1) and caudal to the prefrontal cortex. This region, which is subdivided into rostral [pre‐dorsal premotor cortex (pre‐PMd)] and caudal [dorsal premotor cortex proper (PMd)] components, probably plays a central role in planning and executing actions to achieve a behavioural goal. In the present study, we investigated the functional specializations of the pre‐PMd, PMd, and M1, because the synthesis of the specific functions performed by each area is considered to be essential. Neurons were recorded while monkeys performed a conditional visuo‐goal task designed to include separate processes for determining a behavioural goal (reaching towards a right or left potential target) on the basis of visual object instructions, specifying actions (direction of reaching) to be performed on the basis of the goal, and preparing and executing the action. Neurons in the pre‐PMd and PMd retrieved and maintained behavioural goals without encoding the visual features of the visual object instructions, and subsequently specified the actions by multiplexing the goals with the locations of the targets. Furthermore, PMd and M1 neurons played a major role in representing the action during movement preparation and execution, whereas the contribution of the pre‐PMd progressively decreased as the time of the actual execution of the movement approached. These findings revealed that the multiple processing stages necessary for the realization of an action to accomplish a goal were implemented in an area‐specific manner across a functional gradient from the pre‐PMd to M1 that included the PMd as an intermediary.

Visuomotor signals for reaching movements in the rostro‐dorsal sector of the monkey thalamic reticular nucleus

The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. This unique connectivity suggests that the TRN plays a pivotal role in regulating information flow through the thalamus. Here, we analyzed the roles of TRN neurons in visually guided reaching movements. We first used retrograde transneuronal labeling with rabies virus, and showed that the rostro‐dorsal sector of the TRN (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a visuomotor task. We found that neurons in the TRNrd and PMv showed visual‐, set‐, and movement‐related activity modulation. These results indicate that the TRNrd, as well as the PMv, is involved in the reception of visual signals and in the preparation and execution of reaching movements. The fraction of neurons that were non‐selective for the location of visual signals or the direction of reaching movements was greater in the TRNrd than in the PMv. Furthermore, the fraction of neurons whose activity increased from the baseline was greater in the TRNrd than in the PMv. The timing of activity modulation of visual‐related and movement‐related neurons was similar in TRNrd and PMv neurons. Overall, our data suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs that are predominantly devoid of spatial selectivity, and that these signals modulate how these nuclei engage in both sensory processing and motor output during visually guided reaching behavior.

Involvement of subareas within the dorsal premotor area (PMd) in a conceptually demanding visuomotor task

The aim of this study was to identify the origin of multisynaptic inputs from the GPi to two sectors of the PMd. We injected rabies virus into the rostral (F2r) or caudal part (F2c) of the PMd in macaque monkeys. The virus was transported across synapses from postsynaptic to presynaptic neurons. After a 3-day postinjection period that allows for the second-order neuron labeling, the GPi contained labeled neurons. There was a difference in the distribution area of neuronal labeling between the two injection cases. After the F2r injection, labeled GPi neurons were found in the associative territory. By contrast, the F2c injection led to labeling of the motor territory. The present results revealed that F2r and F2c participate in the associative or motor loop, respectively, suggesting a distinct involvement of these regions in motor planning versus execution.