Slow-wave activity homeostasis in the somatosensory cortex after spinal cord injury.

The cortical reorganization after spinal cord injury (SCI) involves a series of physiological changes that drive the expansion of the intact cortical area to the deafferented cortical area. These changes have always been studied under a stimulus-response paradigm, which demonstrates that the deafferented cortex becomes more responsive to stimulation of body regions above the level of the lesion. However, less is known about how permanent large-scale deafferentation affects spontaneous activity in the somatosensory cortex, an important physiological feature related to the processing of peripheral inputs and perception. Here we studied the spontaneous activity at two sites of the somatosensory cortex, corresponding to forepaw and hindpaw, and at three different time points after SCI: acute SCI, one week post-SCI and chronic SCI (1-3 months after injury). Electrophysiological recordings from anesthetized rats were obtained in conditions of slow-wave activity in order to compare features of the neural populations in periods of cortical up-states. Our data demonstrate that acute SCI reduces the excitability of cortical neurons during up-states in both the forepaw and the hindpaw cortex. One week after SCI, the properties of cortical neurons were similar to those under control conditions, indicating a homeostatic plasticity. Finally, chronic SCI increased neural activity during up-states, while reduced up-state frequency in the cortex. We conclude that SCI induces different homeostatic changes in cortical slow-wave depending on the time after lesion. This temporal evolution of spontaneous activity could help better understand the cortical plasticity associated with acute or chronic SCI.

Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease.

Transcranial static magnetic field stimulation (tSMS) is a recent low-cost non-invasive brain stimulation technique that decreases cortical excitability in healthy subjects. The objective of the present study was to test the ability of tSMS to modulate cortical excitability in patients with Parkinson's disease. We performed a randomized double-blind sham-controlled cross-over study to assess cortical excitability before and immediately after tSMS (or sham) applied for 10 min to the more affected motor cortex of patients with Parkinson's disease. Cortical excitability was quantified by the amplitude of motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). tSMS significantly decreased MEP amplitudes in patients OFF medication (after overnight withdrawal of dopaminergic drugs), but not ON medication (after an acute dose of levodopa). The between-patients variability of tSMS-induced changes was significantly greater ON medication. The variability ON medication could be partly explained by disease progression, i.e. the more advanced the patient, the more likely it was to observe a switch from inhibitory tSMS plasticity OFF medication to paradoxical facilitatory plasticity ON medication. These results suggest that tSMS induces dopamine-dependent changes of cortical excitability in patients with Parkinson's disease.

Increased responses in the somatosensory thalamus immediately after spinal cord injury.

Spinal cord injury (SCI) involves large-scale deafferentation of supraspinal structures in the somatosensory system, producing well-known long-term effects at the thalamo-cortical level. We recently showed that SCI provokes immediate changes in cortical spontaneous and evoked responses and here, we have performed a similar study to define the immediate changes produced in the thalamic ventro-postero-lateral nucleus (VPL) that are associated with the forepaw and hindpaw circuits. Extracellular electrophysiological recordings from the VPL reflected the spontaneous activity and the responses to peripheral electrical stimulation applied to the paws. Accordingly, the activity of the neuronal populations recorded at specific thalamic locations that correspond to the forepaw and hindpaw circuits was recorded under control conditions and immediately after thoracic SCI. The results demonstrate that peripheral inputs from both extremities overlap on neuronal populations in the somatosensory thalamus. In addition, they show that the responses of thalamic neurons to forepaw and hindpaw stimuli are increased immediately after SCI, in association with a specific decrease in spontaneous activity in the hindpaw locations. Finally, the increased thalamic responses after SCI have a state-dependent component in relation with cortical activity. Together, our results indicate that the thalamic changes occurring immediately after SCI could contribute to the cortical changes also detected immediately after such spinal lesions.

Safety Study of Transcranial Static Magnetic Field Stimulation (tSMS) of the Human Cortex.

BACKGROUND: Transcranial static magnetic field stimulation (tSMS) in humans reduces cortical excitability. OBJECTIVE: The objective of this study was to determine if prolonged tSMS (2 h) could be delivered safely in humans. Safety limits for this technique have not been described. METHODS: tSMS was applied for 2 h with a cylindric magnet on the occiput of 17 healthy subjects. We assessed tSMS-related safety aspects at tissue level by measuring levels of neuron-specific enolase (NSE, a marker of neuronal damage) and S100 (a marker of glial reactivity and damage). We also included an evaluation of cognitive side effects by using a battery of visuomotor and cognitive tests. RESULTS: tSMS did not induce any significant increase in NSE or S100. No cognitive alteration was detected. CONCLUSIONS: Our data indicate that the application of tSMS is safe in healthy human subjects, at least within these parameters.

Increased cortical responses to forepaw stimuli immediately after peripheral deafferentation of hindpaw inputs.

Both central and peripheral injuries of the nervous system induce dramatic reorganization of the primary somatosensory cortex. We recently showed that spinal cord injuries at thoracic level in anesthetized rats can immediately increase the responses evoked in the forepaw cortex by forepaw stimuli (above the level of the lesion), suggesting that the immediate cortical reorganization after deafferentation can extend across cortical representations of different paws. Here we show that a complete deafferentation of inputs from the hindpaw induced by injury or pharmacological block of the peripheral nerves in anesthetized rats also increases the responses evoked in the forepaw cortex by forepaw stimuli. This increase of cortical responses after peripheral deafferentation is not associated with gross alterations in the state of cortical spontaneous activity. The results of the present study, together with our previous works on spinal cord injury, suggest that the forepaw somatosensory cortex is critically involved in the reorganization that starts immediately after central or peripheral deafferentation of hindpaw inputs.

Cortical reorganization after spinal cord injury: always for good?

Plasticity constitutes the basis of behavioral changes as a result of experience. It refers to neural network shaping and re-shaping at the global level and to synaptic contacts remodeling at the local level, either during learning or memory encoding, or as a result of acute or chronic pathological conditions. 'Plastic' brain reorganization after central nervous system lesions has a pivotal role in the recovery and rehabilitation of sensory and motor dysfunction, but can also be "maladaptive". Moreover, it is clear that brain reorganization is not a "static" phenomenon but rather a very dynamic process. Spinal cord injury immediately initiates a change in brain state and starts cortical reorganization. In the long term, the impact of injury - with or without accompanying therapy - on the brain is a complex balance between supraspinal reorganization and spinal recovery. The degree of cortical reorganization after spinal cord injury is highly variable, and can range from no reorganization (i.e. "silencing") to massive cortical remapping. This variability critically depends on the species, the age of the animal when the injury occurs, the time after the injury has occurred, and the behavioral activity and possible therapy regimes after the injury. We will briefly discuss these dependencies, trying to highlight their translational value. Overall, it is not only necessary to better understand how the brain can reorganize after injury with or without therapy, it is also necessary to clarify when and why brain reorganization can be either "good" or "bad" in terms of its clinical consequences. This information is critical in order to develop and optimize cost-effective therapies to maximize functional recovery while minimizing maladaptive states after spinal cord injury.

Functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection in rats.

Spinal cord injury may produce long-term reorganization of cortical circuits. Little is known, however, about the early neurophysiological changes occurring immediately after injury. On the one hand, complete thoracic spinal cord transection of the spinal cord immediately decreases the level of cortical spontaneous activity and increases the cortical responses to stimuli delivered to the forepaw, above the level of the lesion. On the other hand, a thoracic spinal cord hemisection produces an immediate cortical hyperexcitability in response to preserved spinothalamic inputs from stimuli delivered to the hindpaw, below the level of the lesion. Here we show that a thoracic spinal cord hemisection also produces a bilateral increase of the responses evoked in the forepaw cortex by forepaw stimuli, associated with a bilateral decrease of cortical spontaneous activity. Importantly, the increased cortical forepaw responses are immediate in the cortex contralateral to the hemisection (significant within 30min after injury), but they are progressive in the cortex ipsilateral to the hemisection (reaching significance only 2.5h after injury). Conversely, the decreased cortical spontaneous activity is progressive both ipsilaterally and contralaterally to the hemisection (again reaching significance only 2.5h after injury). In synthesis, the present work reports a functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection, which is likely important to fully understand the mechanisms underlying long-term cortical reorganization after incomplete spinal cord injuries.

Imaging the spatio-temporal dynamics of supragranular activity in the rat somatosensory cortex in response to stimulation of the paws.

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli.

CB1 receptor antagonism/inverse agonism increases motor system excitability in humans.

CB1 receptor is highly expressed in cerebral structures related to motor control, such as motor cortex, basal ganglia and cerebellum. In the spinal cord, the expression of CB1 receptors has also been observed in ventral motor neurons, interneurons and primary afferents, i.e., in the cells that may be part of the circuits involved in motor control. It is known that the antagonist/inverse agonist of CB1 receptors Rimonabant penetrates the blood-brain barrier and produces a broad range of central psychoactive effects in humans. Based on the occurrence of central effects in humans treated with Rimonabant and on the location of CB1 receptors, we hypothesized that the application of Rimonabant can also affect the motor system. We tested the effects of a single dose of 20mg of Rimonabant on the excitability of motor cortex and of spinal motor neurons in order to detect a possible drug action on motor system at cortical and spinal levels. For this purpose we use classical protocols of transcranial magnetic and electrical stimulation (TMS and TES). Single and paired pulse TMS and TES were used to assess a number of parameters of cortical inhibition and cortical excitability as well as of the excitability of spinal motor neurons. We demonstrated that a single oral dose of 20mg of Rimonabant can increase motor system excitability at cortical and spinal levels. This opens new avenues to test the CB1R antagonists/inverse agonists for the treatment of a number of neurological dysfunctions in which can be useful to increase the excitability levels of motor system. Virtually all the disorders characterized by a reduced output of the motor cortex can be included in the list of the disorders that can be treated using CB1 antagonists/reverse agonists (e.g. stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, fatigue syndromes, parkinsonisms, etc.).

Spinal direct current stimulation modulates the activity of gracile nucleus and primary somatosensory cortex in anaesthetized rats.

Afferent somatosensory activity from the spinal cord has a profound impact on the activity of the brain. Here we investigated the effects of spinal stimulation using direct current, delivered at the thoracic level, on the spontaneous activity and on the somatosensory evoked potentials of the gracile nucleus, which is the main entry point for hindpaw somatosensory signals reaching the brain from the dorsal columns, and of the primary somatosensory cortex in anaesthetized rats. Anodal spinal direct current stimulation (sDCS) increased the spontaneous activity and decreased the amplitude of evoked responses in the gracile nucleus, whereas cathodal sDCS produced the opposite effects. At the level of the primary somatosensory cortex, the changes in spontaneous activity induced by sDCS were consistent with the effects observed in the gracile nucleus, but the changes in cortical evoked responses were more variable and state dependent. Therefore, sDCS can modulate in a polarity-specific manner the supraspinal activity of the somatosensory system, offering a versatile bottom-up neuromodulation technique that could potentially be useful in a number of clinical applications.

Spinal cord injury immediately decreases anesthetic requirements in rats.

STUDY DESIGN: Pharmacologically blocking the spinal cord produces sedative effects and reduces anesthesia requirements in patients and animals. Whether spinal cord injury also reduces anesthesia requirements remains unclear. METHODS: We retrospectively analyzed data from urethane-anesthetized rats (15) to assess anesthesia requirements immediately after complete thoracic transection of the spinal cord. The depth of anesthesia was monitored up to 12 h after spinal transection by the reflexes to noxious stimuli and by electrophysiological recordings from the infragranular layers of the primary somatosensory cortex. Whenever animals displayed electrophysiological and/or behavioral signs of activation, we delivered an additional dose of anesthesia. Anesthetic requirements in animals receiving spinal transection (n=11) were compared with control animals receiving 'sham' lesion (n=9). RESULTS: The cumulative dose necessary to maintain a stable level of anesthesia was significantly lower in transected animals compared with control animals. By about 7 h after spinal cord injury, on average the cumulative dose of urethane was only 1.13±0.14 of the original dose, compared with 1.64±0.19 of the original dose in control animals. CONCLUSIONS: Spinal transection immediately decreased anesthetic requirements in rats. To establish whether these results are relevant for patients with spinal cord injury will require further investigation.

Studying plasticity of sensory function: insight from pregnancy.

Plasticity of sensory function has become an object of study because of its proposed role in the recovery of function after central nervous system damage. Normal pregnancy may provide a useful in vivo model to study the effects of progressive reduction in the abdominal skin receptor density. As such changes are confined to abdominal skin, other parts of the body are only moderately affected by pregnancy and therefore can provide a control for other changes during pregnancy. The two-point discrimination test (TPDT) of the skin is a simple test of the sensory function. We conducted the TPDT in a pregnant population longitudinally studied at different pregnancy stages and in different skin regions. In this pregnant population, we found a reduction in sensory sensibility that was not skin region specific. In particular, the increase in abdominal circumference did not produce different effects of TPDT on the belly compared to the dorsum or the hand. This suggests that the sensory system is able to compensate for the reduction in peripheral information flow through central nervous system plasticity.

Cortical hyperexcitability in response to preserved spinothalamic inputs immediately after spinal cord hemisection.

Chronic injury of the main somatosensory pathways ascending along the spinal cord - the dorsal columns and the spinothalamic tract - can produce both changes in the organization of cortical somatotopic maps and neuropathic pain. Little is known, however, about the early neurophysiological changes occurring immediately after injury. We bilaterally recorded the neural activity of the hindpaw representation of the primary somatosensory cortex evoked by stimuli delivered to the hindpaws before and immediately after a thoracic spinal cord hemisection in anesthetized rats. This unilateral spinal cord injury allowed us to separately investigate the cortical effects of deafferenting the dorsal column (stimuli ipsilateral to the hemisection) or the spinothalamic tract (stimuli contralateral to the hemisection). The hemisection produced immediate bilateral changes in the cortical responses evoked by stimuli delivered to the hindpaw ipsilateral to the hemisection (deafferented dorsal column): an expected loss of classical short-latency cortical responses, accompanied by an unexpected appearance of long-latency activations. At the population level, these activations reflected a progressive stimulus-induced transition of the hindpaw somatosensory cortex from up-and-down states to a sustained activated state. At the single-cell level, these cortical activations resembled the "wind-up" typically observed - with the same type of stimuli - in the dorsal horn cells originating the spinothalamic tract. Virtually no changes were observed in the responses evoked by stimuli delivered to the hindpaw contralateral to the hemisection (deafferented spinothalamic tract). These results suggest that spinal cord hemisection immediately produces an abnormal hyperexcitability of the primary somatosensory cortex in response to preserved spinothalamic inputs from the hindpaw. This immediate cortical hyperexcitability could be important to understand the long-term development of cortical reorganization and neuropathic pain after incomplete spinal cord lesions.

General Poisson exact breakdown of the mutual information to study the role of correlations in populations of neurons.

We present an integrative formalism of mutual information expansion, the general Poisson exact breakdown, which explicitly evaluates the informational contribution of correlations in the spike counts both between and within neurons. The formalism was validated on simulated data and applied to real neurons recorded from the rat somatosensory cortex. From the general Poisson exact breakdown, a considerable number of mutual information measures introduced in the neural computation literature can be directly derived, including the exact breakdown (Pola, Thiele, Hoffmann, & Panzeri, 2003), the Poisson exact breakdown (Scaglione, Foffani, Scannella, Cerutti, & Moxon, 2008) the synergy and redundancy between neurons (Schneidman, Bialek, & Berry, 2003), and the information lost by an optimal decoder that assumes the absence of correlations between neurons (Nirenberg & Latham, 2003; Pola et al., 2003). The general Poisson exact breakdown thus offers a convenient set of building blocks for studying the role of correlations in population codes.

Prefrontal hemodynamic changes produced by anodal direct current stimulation.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been investigated for the treatment of many neurological or neuropsychiatric disorders. Its main effect is to modulate the cortical excitability depending on the polarity of the current applied. However, understanding the mechanisms by which these modulations are induced and persist is still an open question. A possible marker indicating a change in cortical activity is the subsequent variation in regional blood flow and metabolism. These variations can be effectively monitored using functional near-infrared spectroscopy (fNIRS), which offers a noninvasive and portable measure of regional blood oxygenation state in cortical tissue. We studied healthy volunteers at rest and evaluated the changes in cortical oxygenation related to tDCS using fNIRS. Subjects were tested after active stimulation (12 subjects) and sham stimulation (10 subjects). Electrodes were applied at two prefrontal locations; stimulation lasted 10 min and fNIRS data were then collected for 20 min. The anodal stimulation induced a significant increase in oxyhemoglobin (HbO(2)) concentration compared to sham stimulation. Additionally, the effect of active 10-min tDCS was localized in time and lasted up to 8-10 min after the end of the stimulation. The cathodal stimulation manifested instead a negligible effect. The changes induced by tDCS on HbO(2), as captured by fNIRS, agreed with the results of previous studies. Taken together, these results help clarify the mechanisms underlying the regional alterations induced by tDCS and validate the use of fNIRS as a possible noninvasive method to monitor the neuromodulation effect of tDCS.

Spike timing, spike count, and temporal information for the discrimination of tactile stimuli in the rat ventrobasal complex.

The aim of this work was to investigate the role of spike timing for the discrimination of tactile stimuli in the thalamic ventrobasal complex of the rat. We applied information-theoretic measures and computational experiments on neurophysiological data to test the ability of single-neuron responses to discriminate stimulus location and stimulus dynamics using either spike count (40 ms bin size) or spike timing (1 ms bin size). Our main finding is not only that spike timing provides additional information over spike count alone, but specifically that the temporal aspects of the code can be more informative than spike count in the rat ventrobasal complex. Virtually all temporal information--i.e., information exclusively related to when the spikes occur--is conveyed by first spikes, arising mostly from latency differences between the responses to different stimuli. Although the imprecision of first spikes (i.e., the jitter) is highly detrimental for the information conveyed by latency differences, jitter differences can contribute to temporal information, but only if latency differences are close to zero. We conclude that temporal information conveyed by spike timing can be higher than spike count information for the discrimination of somatosensory stimuli in the rat ventrobasal complex.

Modulation of beta oscillations in the subthalamic area during action observation in Parkinson's disease.

Mapping observed actions into the onlooker's motor system seems to provide the neurofunctional mechanisms for action understanding. Subthalamic nucleus (STN) local field potential (LFP) recordings in patients with movement disorders disclosed that network oscillations in the beta range are involved in conveying motor and non-motor information across the cortico-basal ganglia-thalamo-cortical loop. This evidence, together with the existence of connections between the STN and cortical areas active during observation of actions performed by other people, suggests that the STN oscillatory activity in specific frequency bands could encode not only motor information, but also information related to action observation. To test this hypothesis we directly recorded STN oscillations through electrodes for deep brain stimulation in patients with Parkinson's disease during observation of actions and of static objects. We found selective action-related oscillatory modulations in two functionally distinct beta bands: whereas low-beta oscillations (10-18 Hz) selectively desynchronized only during action-observation, high-beta oscillations (20-30 Hz) synchronized both during the observation of action and action-related objects. Low-beta modulations are therefore specific to action observation and high-beta modulations are related to the action scene. Our findings show that in the basal ganglia there are functional changes spreading to the action environment, probably presetting the motor system in relation to the motor context and suggesting that the dynamics of beta oscillations can contribute to action understanding mechanisms.

Responses of infragranular neurons in the rat primary somatosensory cortex to forepaw and hindpaw tactile stimuli.

Infragranular layers constitute the main output of the primary somatosensory cortex and represent an important stage of cortico-cortical and cortico-subcortical integration. We have previously used chronic multiple single-unit recordings to study the spatiotemporal structure of tactile responses of infragranular neurons within the forepaw cortical representation in rats [Tutunculer B, Foffani G, Himes BT, Moxon KA (2006) Structure of the excitatory receptive fields of infragranular forelimb neurons in the rat primary somatosensory cortex responding to touch. Cereb Cortex 16:791-810]. Here we extend our understanding of this structure by studying the overlap between the forepaw and hindpaw cortical representations. We recorded 204 responsive neurons in chronic experiments from eight anesthetized rats. Overall, only 23% of neurons responded exclusively to one paw, 52% of neurons responded to two paws, 19% of neurons responded to three paws, and 5% of neurons responded to all four paws. Quantitative measures of response magnitudes and latencies revealed the following main results. (1) The responses of forepaw neurons overall displayed greater magnitudes and shorter latencies than the responses of hindpaw neurons. (2) The responses to ipsilateral stimuli displayed smaller magnitudes, and longer-and more variable-latencies than the responses to contralateral stimuli. (3) The responses of forepaw neurons to hindpaw stimuli displayed smaller magnitudes and longer latencies than the responses to forepaw stimuli, whereas the responses of hindpaw neurons to forepaw stimuli displayed smaller magnitudes but similar latencies compared with the responses to hindpaw stimuli. These results show that the spatiotemporal structure of tactile responses of infragranular neurons extends across all four paws, and provide the basic architecture for studying physiological integration and pathophysiological reorganization of tactile information in the infragranular layers of the rat primary somatosensory cortex.

Subthalamic local field potential oscillations during ongoing deep brain stimulation in Parkinson's disease.

How deep brain stimulation (DBS) acts and how the brain responds to it remains unclear. To investigate the mechanisms involved, we analyzed changes in local field potentials from the subthalamic area (STN-LFPs) recorded through the deep brain macroelectrode during monopolar DBS of the subthalamic nucleus area (STN-DBS) in a group of eight patients (16 nuclei) with idiopathic Parkinson's disease. Monopolar STN-DBS was delivered through contact 1 and differential LFP recordings were acquired between contacts 0 and 2. The stimulating contact was 0.5 mm away from each recording contact. The power spectral analysis of STN-LFPs showed that during ongoing STN-DBS whereas the power of beta oscillations (8-20 Hz) and high beta oscillations (21-40 Hz) remained unchanged, the power of low-frequency oscillations (1-7 Hz) significantly increased (baseline=0.37+/-0.22; during DBS=7.07+/-15.10, p=0.0003). Despite comparable low-frequency baseline power with and without levodopa, the increase in low-frequency oscillations during STN-DBS was over boosted by pretreatment with levodopa. The low-frequency power increase in STN-LFPs during ongoing STN-DBS could reflect changes induced at basal ganglia network level similar to those elicited by levodopa. In addition, the correlation between the heart beat and the low-frequency oscillations suggests that part of the low-frequency power increase during STN-DBS arises from polarization phenomena around the stimulating electrode. Local polarization might in turn also help to normalize STN hyperactivity in Parkinson's disease.

Mutual information expansion for studying the role of correlations in population codes: how important are autocorrelations?

The role of correlations in the activity of neural populations responding to a set of stimuli can be studied within an information theory framework. Regardless of whether one approaches the problem from an encoding or decoding perspective, the main measures used to study the role of correlations can be derived from a common source: the expansion of the mutual information. Two main formalisms of mutual information expansion have been proposed: the series expansion and the exact breakdown. Here we clarify that these two formalisms have a different representation of autocorrelations, so that even when the total information estimated differs by less than 1%, individual terms can diverge. More precisely, the series expansion explicitly evaluates the informational contribution of autocorrelations in the count of spikes, that is, count autocorrelations, whereas the exact breakdown does not. We propose a new formalism of mutual information expansion, the Poisson exact breakdown, which introduces Poisson equivalents in order to explicitly evaluate the informational contribution of count autocorrelations with no approximation involved. Because several widely employed manipulations of spike trains, most notably binning and pooling, alter the structure of count autocorrelations, the new formalism can provide a useful general framework for studying the role of correlations in population codes.