In the present study, we recorded single neurons in the premotor cortex of rhesus monkeys while they were preparing for a trained motor movement or performing an untrained action. In addition, we also recorded the activity of these neurons during observation of a video stimulus containing a grasping motion.
We found that the premotor cortex neurons activated during observation of a motor act (mirror neurons) were spatially selective, with about half preferring either the monkey’s peripersonal or extrapersonal space. Some of these neurons encode space according to a metric representation, while others code space in operational terms.
Grasping
Grasping is an act of taking, holding, or seizing firmly with (or as if with) the hand. It is a natural reflex in newborns. It is also often associated with reaching and eye control and gaze.
During grasping, there is an increased activity of the mirror neurons. These neurons are used for action understanding and motor analysis, as well as to understand the actions of other animals or objects. They are thought to fire when they detect a motor action that another neuron has just activated in the same area of the brain. This activated neuron can then trigger a similar activation in another area of the brain that has been observed, helping the observer monkey to understand the action or object.
In contrast to the neuronal response to target stimuli, the LC response to nontarget cues was smaller in easy/fast and difficult tasks (Figs. 2-4). This response was more pronounced in the difficult task than in the easy/fast task and occurred during both task performance and passive stimulation.
These differences were significant when compared to the psychometric slopes and DA values. However, the difference was not significant when comparing a group of CS that predicted reward alone to those that predicted reward plus optical stimulation (p = 0.015).
The LC neurons had small cutaneous receptive fields, confined to the glabrous skin of one fingertip in each VPL neuron. Despite the small receptive field, these neurons were capable of recording neuronal responses with both QA and SA properties.
This is important because the LC is involved in both the processing of visual information and the control of movement. It is possible that the LC could be responsible for coordinating the movement of the fingers during grasping.
Grasping is important in both communication and learning. During conversation, people often grasp the meaning of what they are saying and make sure that they fully understand it before they let go of it. This helps them to avoid confusion or misunderstandings, which can lead to a variety of negative effects on the interaction. Similarly, during learning, people will grasp the details of new information, and they will use that information to help them learn the rest of the subject.
Interaction
During interaction, the monkey must consider many factors and use a variety of cognitive processes to understand what is happening around it. This is done by observing other monkeys and interacting with them, or even by performing actions on their own.
Monkeys can also be observed grooming one another, or using their teeth to pick up dirt, bugs and debris from their fur. These behaviors, which are highly social in nature, help the monkey understand how it is interacting with others and infer its own social rank within the group.
The brain of the monkey has a special circuit dedicated to social interactions, and researchers recently discovered that viewing videos of these social interactions lit up this network. They believe this network may have a similar function to human brains’ social circuitry.
In this study, four rhesus macaques watched videos of social and physical interactions, and then underwent functional magnetic resonance imaging. This allowed them to detect which parts of the brain were stimulated by which types of interactions.
For example, when a monkey viewed videos of other monkeys interacting with each other or other animals, two areas in the brain that help with face and body recognition were activated. However, when the monkey viewed videos of other monkeys performing tasks on their own, or of different types of physical interactions between inanimate objects, these regions were not activated.
When a monkey saw a video of someone grasping food, it activated neurons in the premotor cortex that are activated by both the execution and the observation of motor acts (mirror neurons). Mirror neurons preferentially encode space relative to the monkey: about half of them encode peripersonal space while another half encode extrapersonal space. Some of these mirror neurons encode space according to a metric representation, while others encode space in operational terms.
To study the activity of these spatially selective mirror neurons, we asked a monkey to observe movies showing the same grasping motor act from three different views: the subjective perspective 0deg, lateral 90 deg and frontal 180 deg perspectives. Then, we recorded the activity of mirror neurons in both F5 and AIP when the monkey was shown the movie from each of the vantage points. This allowed us to show that about 20% of the mirror neurons in both F5 and AIP responded in equal proportion to the observations from each vantage point.
Detection
Detection of a stimulus is an essential component of many cognitive processes (Morris and MacGill 2006; Posner and Gelade 1980). Neural activation during detection is known to increase visuospatial attention, enhancing the ability to detect and discriminate stimuli that are within a specific visual field. Moreover, these effects are likely to be more pronounced in higher intelligence animals. Nonetheless, the precise mechanisms by which neuron activation enhances this capacity remain to be determined.
The monkeys used in this study were trained to perform a sensory detection task using tactile stimulation. The probe tip was indented into the skin with a gentle pressure, resulting in a small voltage spike that stimulated LC neurons. Trials were repeated until the monkey pressed an illuminated button that corresponded to the stimulus. The monkey was then rewarded for performing the task correctly.
We measured the amplitude of the elicited pulses in the spike trains of LC neurons with an extracellular recording from neurons that were placed near the tip of the probe during each trial. These cells were classified as QA or SA, depending on whether their firing rate increased after the probe touched the skin and returned to its spontaneous rate immediately, or maintained an increasing rate until the probe was lifted off of the skin (Fig. 2 A and C).
VPL neurons were also recorded during the same trial. This was done using 30-mm-diam, preinsulated tungsten wire electrodes that were implanted in the brain through the distal end of a stereotaxically positioned guide cannula. The electrode was moved through the brain in short steps, a process that required the movement of the guide cannula
In this experiment, we observed that VPL activity is faithfully modulated as a function of stimulus amplitude and is thus consistent with psychophysical performance (Fig. 3C). However, this does not account for individual animal decision in individual trials. Nevertheless, our results indicate that the VPL is a crucial part of the somatosensory thalamus in terms of psychophysical performance.
To gain specific optogenetic control of dopamine neurons, we introduced a combination of pAAV9-TH-Cre-SV40 and pAAV5-EYFP-WPRE-pA viral vectors into the nigrostriatal dopaminergic neurons (Fig. 1A). The first vector, pAAV9-TH-Cre-SV40, delivered Cre recombinase under the control of a 300-base Tyrosine Hydroxylase (TH) promoter sequence. The second vector, pAAV5-EYFP-WPRE-pA, delivered an EYFP-WPRE fused to a rat dopamine receptor gene.
Control
In the monkey pars compacta (LC) area, neurons activate during the observation of the same motor act done by a human experimenter or by another monkey (Figure 1B). This category of visuomotor neurons is called mirror neurons. These neurons are most active during the observation of grasping, followed by manipulating and placing. In addition, these neurons also activate when part of the observed movement is obscured (Fig. 2C).
During the presentation of a target stimulus in an easy task, the LC neurons showed short onset latencies and brief activations. For the difficult task, they displayed longer onset latency and longer activations. These behaviors were consistent with the hypothesis that the LC cells produce a high order representation of the visual presentation.
For a probe stimulation paradigm, we used a two-viral vector combination to gain specific optogenetic control of dopamine neurons in the substantia nigra. The first viral vector (pAAV9-TH-Cre-SV40, UPenn Vector Core) delivered Cre recombinase under the control of a 300-base Tyrosine Hydroxylase (TH) promoter sequence to target the dopaminergic cell layer of the substantia nigra.
We then used a separate viral vector (pAAV5-EF1a-dio-hChR2(H123R)-EYFP-WPRE-pA, UNC Vector Core) to deliver an alternative ChR2 construct. This second viral vector was designed to allow for a combination of dopaminergic control and visual stimulation without requiring the use of recombination.
To characterize neuronal response during the detection of target stimuli, we measured firing rate adaptation to a skin indentation (Fig. 2A) and to the amplitude of the stimulus presented (Fig. 2C). We defined a QA group of neurons whose amplitude modulations were stronger for the first pulses, and an SA group of neurons whose amplitude modulations became more sensitive with increasing amplitude (Fig. 3E).
In this type of curve, the probability of detection was determined by fitting a Boltzmann equation. The lower and upper Boltzmann parameters were fixed based on psychometric and neurometric performance in each session. The amplitude modulation of the curve was calculated as the difference between the detection probability and the maximum and minimum amplitudes, allowing for the variation in monkey/neuron performance within the relevant interval.