INFLUENCE OF RAT CENTRAL THALAMIC NEURONS ON FORAGING BEHAVIOR IN A HAZARDOUS ENVIRONMENT

The basolateral amygdala (BL) is a major regulator of foraging behavior. Following BL inactivation, rats become indifferent to predators. However, at odds with the view that the amygdala detects threats and generate defensive behaviors, most BL neurons have reduced firing rates during foraging and at proximity of the predator. In search of the signals determining this unexpected activity pattern, this study considered the contribution of the central medial thalamic nucleus (CMT), which sends a strong projection to BL, mostly targeting its principal neurons. Inactivation of CMT or BL with muscimol abolished the rats’ normally cautious behavior in the foraging task. Moreover, unit recordings revealed that CMT neurons showed large but heterogeneous activity changes during the foraging task, with many neurons decreasing or increasing their discharge rates, with a modest bias for the latter. A generalized linear model revealed that CMT neurons encode many of the same task variables as principal BL cells. However, the nature (inhibitory vs. excitatory) and relative magnitude of the activity modulations seen in CMT neurons differed markedly from those of principal BL cells but were very similar to those of fast-spiking BL interneurons. Together, these findings suggest that, during the foraging task, CMT inputs fire some principal BL neurons, recruiting feedback interneurons in BL, resulting in the widespread inhibition of principal BL cells.

How synaptic strength, short-term plasticity, and temporal factors contribute to neuronal spike output

To compute spiking responses, neurons integrate inputs from thousands of synapses whose strengths span an order of magnitude. Intriguingly, in mouse neocortex, the small minority of 'strong' synapses is found predominantly between similarly tuned cells, suggesting they are the synapses that determine a neuron's spike output. This raises the question of how other computational primitives, such as 'background' activity from the majority of synapses, which are 'weak', short-term plasticity, and temporal synchrony contribute to spiking. First, we combined extracellular stimulation and whole-cell recordings in mouse barrel cortex to map the distribution of excitatory postsynaptic potential (EPSP) amplitudes and paired-pulse ratios of excitatory synaptic connections converging onto individual layer 2/3 (L2/3) neurons. While generally net short-term plasticity was weak, connections with EPSPs > 2 mV displayed pronounced paired-pulse depression. EPSP amplitudes and paired-pulse ratios of connections converging onto the same neurons spanned the full range observed across L2/3 and there was no indication that strong synapses nor those with particular short-term plasticity properties were associated with particular cells, which critically constrains theoretical models of cortical filtering. To investigate how different computational primitives of synaptic information processing interact to shape spiking, we developed a computational model of a pyramidal neuron in the rodent L2/3 circuitry: firing rates and pairwise correlations of presynaptic inputs were constrained by in vivo observations, while synaptic strength and short-term plasticity were set based on our experimental data. Importantly, we found that the ability of strong inputs to evoke spiking critically depended on their high temporal synchrony and high firing rates observed in vivo and on synaptic background activity - and not primarily on synaptic strength, which in turn further enhanced information transfer. Depression of strong synapses was critical for maintaining a neuron's responsivity and prevented runaway excitation. Our results provide a holistic framework of how cortical neurons exploit complex synergies between temporal coding, synaptic properties, and noise in order to transform synaptic inputs into output firing.

Locus Coeruleus Optogenetic Modulation: Lessons Learned from Temporal Patterns

After reviewing seminal studies using optogenetics to interrogate the functional role of the locus coeruleus in behavior, we conclude that differences in firing rates and firing patterns of locus coeruleus neurons contribute to locus coeruleus nucleus heterogeneity by recruiting different output circuitry, and differentially modifying behavior. The outcomes initiated by different optogenetic input activation patterns and frequencies can have opposite consequences for behavior, activate different neurons in the same target structure, be supported by distinct adrenoceptors and vary with behavioral state.

Sensing and decoding the neural drive to paralyzed muscles during attempted movements of a person with tetraplegia using a sleeve array

Motor neurons convey information about motor intent that can be extracted and interpreted to control assistive devices. However, most methods for measuring the firing activity of single neurons rely on implanted microelectrodes. Although intracortical brain-computer interfaces (BCIs) have been shown to be safe and effective, the requirement for surgery poses a barrier to widespread use that can be mitigated by instead using noninvasive interfaces. The objective of this study was to evaluate the feasibility of deriving motor control signals from a wearable sensor that can detect residual motor unit activity in paralyzed muscles after chronic cervical spinal cord injury (SCI). Despite generating no observable hand movement, volitional recruitment of motor units below the level of injury was observed across attempted movements of individual fingers and overt wrist and elbow movements. Subgroups of motor units were coactive during flexion or extension phases of the task. Single digit movement intentions were classified offline from the EMG power (RMS) or motor unit firing rates with median classification accuracies >75% in both cases. Simulated online control of a virtual hand was performed with a binary classifier to test feasibility of real-time extraction and decoding of motor units. The online decomposition algorithm extracted motor units in 1.2 ms, and the firing rates predicted the correct digit motion 88 ± 24% of the time. This study provides the first demonstration of a wearable interface for recording and decoding firing rates of motor units below the level of injury in a person with motor complete SCI.

State-dependent modulation of activity in distinct layer 6 corticothalamic neurons in barrel cortex of awake mice

Layer 6 corticothalamic (L6 CT) neurons are in a strategic position to control sensory input to the neocortex, yet we understand very little about their functions. Apart from studying their anatomical, physiological and synaptic properties, most recent efforts have focused on the activity-dependent influences CT cells can exert on thalamic and cortical neurons through causal optogenetic manipulations. However, few studies have attempted to study them during behavior. In an attempt to address this gap, we performed juxtacellular recordings from optogenetically identified CT neurons in whisker-related primary somatosensory cortex (wS1) of awake, head-fixed mice (of either sex) free to rest quietly or self-initiate bouts of whisking and locomotion. We found a rich diversity of response profiles exhibited by CT cells. Broadly, their spiking patterns were either modulated by whisker-related behavior (~28%) or not (~72%). Whisker-related neurons exhibited both increases as well as decreases in firing rates. We also encountered cells with preceding modulations in firing rate before whisking onset. Overall, whisking better explained these changes in rates than overall changes in arousal. The CT cells that showed no whisker-related activity had low spontaneous firing rates (<0.5 Hz), with many all but silent. Remarkably, this relatively silent population preferentially spiked at the state transition point when pupil diameter constricted and the mouse entered quiet wakefulness. Thus, our results demonstrate that L6 CT neurons in wS1 show diverse spiking patterns, perhaps subserving distinct functional roles related to precisely timed responses during complex behaviors and transitions between discrete waking states.

Bridging the Functional and Wiring Properties of V1 Neurons Through Sparse Coding

The functional properties of neurons in the primary visual cortex (V1) are thought to be closely related to the structural properties of this network, but the specific relationships remain unclear. Previous theoretical studies have suggested that sparse coding, an energy-efficient coding method, might underlie the orientation selectivity of V1 neurons. We thus aimed to delineate how the neurons are wired to produce this feature. We constructed a model and endowed it with a simple Hebbian learning rule to encode images of natural scenes. The excitatory neurons fired sparsely in response to images and developed strong orientation selectivity. After learning, the connectivity between excitatory neuron pairs, inhibitory neuron pairs, and excitatory-inhibitory neuron pairs depended on firing pattern and receptive field similarity between the neurons. The receptive fields (RFs) of excitatory neurons and inhibitory neurons were well predicted by the RFs of presynaptic excitatory neurons and inhibitory neurons, respectively. The excitatory neurons formed a small-world network, in which certain local connection patterns were significantly overrepresented. Bidirectionally manipulating the firing rates of inhibitory neurons caused linear transformations of the firing rates of excitatory neurons, and vice versa. These wiring properties and modulatory effects were congruent with a wide variety of data measured in V1, suggesting that the sparse coding principle might underlie both the functional and wiring properties of V1 neurons.

A transcriptional constraint mechanism limits the homeostatic response to activity deprivation in mammalian neocortex

Healthy neuronal networks rely on homeostatic plasticity to maintain stable firing rates despite changing synaptic drive. These mechanisms, however, can themselves be destabilizing if activated inappropriately or excessively. For example, prolonged activity deprivation can lead to rebound hyperactivity and seizures. While many forms of homeostasis have been described, whether and how the magnitude of homeostatic plasticity is constrained remains unknown. Here we uncover negative regulation of cortical network homeostasis by PAR bZIP family of transcription factors. In their absence the network response to prolonged activity withdrawal is too strong and this is driven by exaggerated upregulation of recurrent excitatory synaptic transmission. These data indicate that transcriptional activation is not only required for many forms of homeostatic plasticity but is also involved in restraint of the response to activity deprivation.

The Effect of Local Cooling at the Elbow on Nerve Conduction Velocity and Motor Unit Behaviour: An Exploration of a Novel Neurological Assessment

Background: This study aimed to determine the effects of a standard therapeutic cooling protocol using crushed ice on the elbow to explore if changes in the motor unit (MU) firing rates in the first dorsal interosseous (FDI) muscle are comparable to known changes in sensory and motor nerve conduction velocity (NCV) due to a regional temperature drop around a peripheral nerve. Methods: Twelve healthy individuals were assessed before cooling, immediately after cooling, and 15 min of rewarming. Assessments included two standard non-invasive nerve conduction velocity tests and a non-invasive investigation of the MU firing rates using surface electromyography decomposition (dEMG). Results: Repeated ANOVAs showed significant differences in the MU firing rates and NCV between time points (p = 0.01 and p < 0.001). All measures showed significant differences between pre and post cooling and between pre-cooling and 15 min of passive re-warming, however, no changes were seen between post cooling and rewarming except in the sensory NCV, which increased but did not return to the pre-cooled state. Conclusions: This current study showed a significant, temporary, and reversible reduction in ulnar NCV across the elbow in healthy subjects, which was associated with a significant decrease in mean MU firing rates in the FDI muscle.