Yifat Prut

Primate spinal interneurons show pre-movement instructed delay activity

Preparatory changes in neural activity before the execution of a movement have been documented in tasks that involve an instructed delay period (an interval between a transient instruction cue and a subsequently triggered movement). Such preparatory activity occurs in many motor centres in the brain, including the primary motor cortex, premotor cortex, supplementary motor area and basal ganglia. Activity during the instructed delay period reflects movement planning, as it correlates with parameters of the cue and the subsequent movement (such as direction and extent), although it occurs well before muscle activity. How such delay-period activity shapes the ensuing motor action remains unknown. Here we show that spinal interneurons also exhibit early pre-movement delay activity that often differs from their responses during the subsequent muscle activity. This delay activity resembles the set-related activity found in various supraspinal areas, indicating that movement preparation may occur simultaneously over widely distributed regions, including spinal levels. Our results also suggest that two processes occur in the spinal circuitry during this delay period: the motor network is primed with rate changes in the same direction as subsequent movement-related activity; and a superimposed global inhibition suppresses the expression of this activity in muscles.

Population responses to multifrequency sounds in the cat auditory cortex: one- and two-parameter families of sounds

Population responses to multi-frequency sounds were recorded in primary auditory cortex of anesthetized cats. The sounds consisted of single-tone stimuli; two-tone stimuli; and nine-tone stimuli, with the tones evenly spaced on a linear frequency scale. The stimuli were presented through a sealed, calibrated sound delivery system. Single units, cluster activity (CA) and the short-time mean absolute value of the envelope of the neural signal (MABS) were recorded extracellularly from six microelectrodes simultaneously. The CA and MABS were interpreted as measures of the activity of large populations of neurons, in contrast with the single unit activity which is presumably recorded from single neurons. The responses of the MABS signal to simple stimuli were generally similar to those of the CA, but were more stable statistically. Thus, the MABS is better suited for studying the activity of populations of neurons. The responses to tones near the best frequency were strongly influenced by a second tone, even when the second tone was outside the single-tone response area. These influences could be both facilitatory and suppressory. They could not be predicted from the responses to single tones. The responses to the nine-tone stimuli could be explained qualitatively by the responses to the two-tone stimuli. It is concluded that the population responses in primary auditory cortex are shaped by the contributions of the individual frequencies appearing in the stimulus and by the interactions between pairs of frequencies. Interactions between stimulus components are therefore a necessary component of any attempt to explain the processing of complex sounds in the auditory cortex. They may play a role in a global representation of the stimulus spectrum in the primary auditory cortex. The presence of higher-order interactions cannot be excluded by the results presented here.

Synchronization of midbrain dopaminergic neurons is enhanced by rewarding events.

The basal ganglia network is divided into two functionally related subsystems: the neuromodulators and the main axis. It is assumed that neuromodulators adjust cortico-striatal coupling. This adjustment might depend on the response properties and temporal interactions between neuromodulators. We studied functional interactions between simultaneously recorded pairs of neurons in the basal ganglia while monkeys performed a classical conditioning task that included rewarding, neutral, and aversive events. Neurons that belong to a single neuromodulator group exhibited similar average responses, whereas main axis neurons responded in a highly diverse manner. Dopaminergic neuromodulators transiently increased trial-to-trial (noise) correlation following rewarding but not aversive events, whereas cholinergic neurons of the striatum decreased their trial-to-trial correlation. These changes in functional connectivity occurred at different epochs of the trial. Thus, the coding scheme of neuromodulators (but not main axis neurons) can be viewed as a single-dimensional code that is further enriched by dynamic neuronal interactions.

Temporal Convergence of Dynamic Cell Assemblies in the Striato-Pallidal Network

The basal ganglia (BG) have been hypothesized to implement a reinforcement learning algorithm. However, it is not clear how information is processed along this network, thus enabling it to perform its functional role. Here we present three different encoding schemes of visual cues associated with rewarding, neutral, and aversive outcomes by BG neuronal populations. We studied the response profile and dynamical behavior of two populations of projection neurons [striatal medium spiny neurons (MSNs), and neurons in the external segment of the globus pallidus (GPe)], and one neuromodulator group [striatal tonically active neurons (TANs)] from behaving monkeys. MSNs and GPe neurons displayed sustained average activity to cue presentation. The population average response of MSNs was composed of three distinct response groups that were temporally differentiated and fired in serial episodes along the trial. In the GPe, the average sustained response was composed of two response groups that were primarily differentiated by their immediate change in firing rate direction. However, unlike MSNs, neurons in both GPe response groups displayed prolonged and temporally overlapping persistent activity. The putamen TANs stereotyped response was characterized by a single transient response group. Finally, the MSN and GPe response groups reorganized at the outcome epoch, as different task events were reflected in different response groups. Our results strengthen the functional separation between BG neuromodulators and main axis neurons. Furthermore, they reveal dynamically changing cell assemblies in the striatal network of behaving primates. Finally, they support the functional convergence of the MSN response groups onto GPe cells.

Low-Pass Filter Properties of Basal Ganglia–Cortical–Muscle Loops in the Normal and MPTP Primate Model of Parkinsonism

Oscillatory bursting activity is commonly found in the basal ganglia (BG) and the thalamus of the parkinsonian brain. The frequency of these oscillations is often similar to or higher than that of the parkinsonian tremor, but their relationship to the tremor and other parkinsonian symptoms is still under debate. We studied the frequency dependency of information transmission in the cortex–BG and cortex–periphery loops by recording simultaneously from multiple electrodes located in the arm-related primary motor cortex (MI) and in the globus pallidus (GP) of two vervet monkeys before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment and induction of parkinsonian symptoms. We mimicked the parkinsonian bursting oscillations by stimulating with 35 ms bursts given at different frequencies through microelectrodes located in MI or GP while recording the evoked neuronal and motor responses. In the normal state, microstimulation of MI or GP does not modulate the discharge rate in the other structure. However, the functional-connectivity between MI and GP is greatly enhanced after MPTP treatment. In the frequency domain, GP neurons usually responded equally to 1–15 Hz stimulation bursts in both states. In contrast, MI neurons demonstrated low-pass filter properties, with a cutoff frequency above 5 Hz for the MI stimulations, and below 5 Hz for the GP stimulations. Finally, muscle activation evoked by MI microstimulation was markedly attenuated at frequencies higher than 5 Hz. The low-pass properties of the pathways connecting GP to MI to muscles suggest that parkinsonian tremor is not directly driven by the BG 5–10 Hz burst oscillations despite their similar frequencies.

Functions of mammalian spinal interneurons during movement

The major recent advances in understanding the role of spinal neurons in generating movement include new information about the modulation of classic reflex pathways during fictive locomotion and in response to pharmacological probes. The possibility of understanding movements in terms of spinal representations of a basic set of movement primitives has been extended by the analysis of normal reflexes. Recordings of the activity of cervical interneurons in behaving monkeys has elucidated their contribution to generating voluntary movement and revealed their involvement in movement preparation.

In search of the best stimulus: an optimization procedure for finding efficient stimuli in the cat auditory cortex.

Units in the auditory cortex of cats respond to a large variety of stimuli: pure tones, AM- and FM-modulated signals, clicks, wideband noise, natural sounds, and more. However, no single family of sounds was found to be optimal (in the sense that oriented lines are optimal in the visual cortex). The search for optimal complex sounds is hard because of the high dimensionality of the space of interesting sounds. In an effort to overcome this problem, an automatic search procedure for finding efficient stimuli in high-dimensional sound spaces was developed. This procedure chooses the stimuli to be presented according to the responses to past stimuli, trying to increase the strength of the response. The results of applying this method to recordings of population activity in the primary auditory cortex of cats are described. The search was applied to single tones, two-tone stimuli, four-tone stimuli and to a two-dimensional subset of nine-tone stimuli, parametrized by the center frequency and the fixed difference between adjacent frequencies. The method was able to find efficient stimuli, and its performance improved with the dimension of the sound spaces. Efficient stimuli, found in different optimization runs using population activity recorded from the same electrode, often shared similar frequencies and pairs of frequencies, and tended to evoke similar levels of activity. This result indicates that a global analysis of the location of spectral peaks is performed at the level of the auditory cortex.

Population responses to multifrequency sounds in the cat auditory cortex: Four-tone complexes

Population responses to two-tone and four-tone sounds were recorded in primary auditory cortex of anesthetized cats. The stimuli were delivered through a sealed, calibrated sound delivery system. The envelope of the neural signal (short time mean absolute value, MABS) was recorded extracellularly from six microelectrodes simultaneously. A new method was developed to describe the responses to the four-tone complexes. The responses were represented as sums of contributions of different orders. The first order contributions described the effect of the single frequencies appearing in the stimulus. The second order contributions described the modulatory effect of the pairs of frequencies. Higher order contributions could in principle be computed. This paper concentrates on the mean onset responses. The extent to which the first and second order contributions described the onset responses was assessed in two ways. First, the actual responses to two-tone stimuli were compared with those predicted using the contributions computed from the four-tone stimuli. Second, the residual variance in the responses, after the subtraction of the first and second order contributions, was computed and compared with the variability in the responses to repetitions of the same stimulus. The first type of analysis showed good quantitative agreement between the predicted and the measured two-tone responses. The second type of analysis showed that the first and second order contributions were often sufficient to predict the responses to four-tone stimuli up to the level of the variability in the responses to repetitions of a single stimulus. In conjunction with the results of the companion paper (Nelken et al., 1994a) it is concluded that the onset responses to multifrequency sounds are shaped mainly by the single frequency content of the sound and by two-tone interactions, and that higher order interactions contribute much less to the responses. It follows that single-tone effects and two-tone interactions are necessary and sufficient to explain the mean population onset responses to the four-tone stimuli. More information can be coded in the temporal evolution of the responses.

Encoding by Synchronization in the Primate Striatum

Information is encoded in the nervous system through the discharge and synchronization of single neurons. The striatum, the input stage of the basal ganglia, is divided into three territories: the putamen, the caudate, and the ventral striatum, all of which converge onto the same motor pathway. This parallel organization suggests that there are multiple and competing systems in the basal ganglia network controlling behavior. To explore which mechanism(s) enables the different striatal domains to encode behavioral events and to control behavior, we compared the neural activity of phasically active neurons [medium spiny neurons (MSNs), presumed projection neurons] and tonically active neurons (presumed cholinergic interneurons) across striatal territories from monkeys during the performance of a well practiced task. Although neurons in all striatal territories displayed similar spontaneous discharge properties and similar temporal modulations of their discharge rates to the behavioral events, their correlation structure was profoundly different. The distributions of signal and noise correlation of pairs of putamen MSNs were strongly shifted toward positive correlations and these two measures were correlated. In contrast, MSN pairs in the caudate and ventral striatum displayed symmetrical, near-zero signal and noise correlation distributions. Furthermore, only putamen MSN pairs displayed different noise correlation dynamics to rewarding versus neutral/aversive cues. Similarly, the noise correlation between tonically active neuron pairs was stronger in the putamen than in the caudate. We suggest that the level of synchronization of the neuronal activity and its temporal dynamics differentiate the striatal territories and may thus account for the different roles that striatal domains play in behavioral control.

Getting ready to move: transmitted information in the corticospinal pathway during preparation for movement.

Corticospinal interactions are considered to play a key role in executing voluntary movements. Nonetheless several different studies have shown directly and indirectly that these interactions take place long before movement starts, when preparation for forthcoming movements dominates. When motor-related parameters are continuously processed in several premotor cortical sites, segmental circuitry is directly exposed to this processing via descending pathways which originate from these sites in parallel to descending fibers that derive from primary motor cortex. Recent studies have highlighted the functional role of these interactions in priming downstream elements for the ensuing motor actions. Time-resolved analysis has further emphasized the dynamic properties of pre-movement preparatory activity.