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Jankowski, M. M.

Publications and source records attributed to Jankowski, M. M..

13 recordsLinked to original sources

Predictive abstract task representations support few-shot learning in the rat brain

Few-shot learning reveals core mechanisms of flexible cognition and adaptive decision- making in animal behavior by showing how animals rapidly infer rules, categories, or action strategies from sparse experience. Few-shot learning often depends on abstract representations that capture task structure and generalize across similar instances of the same task. The orbitofrontal cortex (OFC) is known to encode abstract representations, but whether these representations can adapt to new contingencies at the rapid timescale of few-shot learning is unknown. We trained rats on a sequence-learning task with recurring structure but changing contingencies. Rats demonstrated few-shot learning, reaching near-optimal performance within 2-3 rewards after each contingency change, exploiting the tasks recurring structure to rapidly generalize across sequence blocks. We recorded OFC activity using Neuropixels probes during task performance. The firing rate of OFC units in the few seconds preceding each poke encoded the task state and predicted the selected action. Remarkably, this predictive activity also encoded the abstract notion of role: the function of an action under the current contingencies. Role representations in the OFC changed on the same rapid timescale as the behavioral changes. We suggest that few-shot learning in this task is supported by the rapid remapping of roles onto actions.

neuroscience↗

The representation of regularity and randomness in auditory cortex of awake rats

Auditory cortex possesses a remarkable ability to discriminate between tone sequences with different levels of statistical regularities. To examine this phenomenon at the level of single neurons, we recorded responses from auditory cortex of awake rats. The rats passively listened to multitone sequences composed of 4, 5 or 6 tones. The tones could be presented in periodic sequences with a fixed, repeated cycle; in a fully random condition; or in an intermediate condition in which cycles were maintained but tones were randomly permuted within each cycle (random cycle condition). Units showed a continuum of preferences between order-preferring neurons and randomness-preferring neurons. Unexpectedly, we found sensitivity to the position of sounds in the cycle ( phase modulation). The strongest and most consistent phase modulations were in the responses to the random cycle condition. Finally, we show how such sensitivities may emerge from a simple, biologically- plausible computation.

neuroscience↗

Repeated administration of cannabidiol decreases splenic lymphocyte numbers in rats: involvement of CB2 receptors

Cannabidiol (CBD), the major non-psychotropic compound of Cannabis sp., is an effective treatment for inflammatory and autoimmune diseases and produces various anti-tumor effects but the mechanisms of its long-term actions in vivo remain unclear. We have previously shown that CBD administration (5 mg/kg) in healthy rats significantly decreased lymphocyte numbers in peripheral blood, involving B, T CD4+ and T CD8+ lymphocyte subsets, but not natural killer (NK) cells. To examine the effects of CBD on lymphocyte subsets in the spleen and NK cellular cytotoxicity (NKCC), adult male Wistar rats (n = 63) were administered intraperitoneal injections of CBD (2.5 or 5 mg/kg/day) for 14 consecutive days and lymphocyte counts were obtained using flow cytometry. NKCC in the peripheral blood and spleen was quantified using a Chromium-51 release assay. Furthermore, CB2 receptors were blocked using selective receptor antagonist AM630 (1 mg/kg). The results indicate that repeated administration of CBD at a dose of 5 mg/kg/day resulted in a decrease in splenic lymphocyte number, involving T and B lymphocytes but not NK cells. The decrease in lymphocyte number was partially blocked by pretreatment with CB2 receptor antagonist while no changes in NKCC were observed following CBD administration. These results reveal that in healthy rats, CBD produces similar lymphopenic effects in the spleen as it does in peripheral blood and that the effects of CBD on lymphocyte numbers in vivo are at least partially mediated by CB2 receptors.

immunology↗

Insular cortex encodes task alignment

Animals can learn complex behaviors. Animal behavior in the lab has traditionally been studied via summary statistics such as trial-based success rates. However, animal behavior is much more fine-grained: a trial in an experiment often consists of multiple actions, and more than one strategy can lead to a successful completion of a trial. To understand how the brain controls behavior, a fine-grained yet compact description of behavior is necessary. We describe here an approach for estimating the strategies animals use for a large family of tasks from first principles. Using reinforcement learning with informational constraints on policies, we compute a rich set of candidate policies with a small number of meaningful parameters, and match observed behavior to these policies. In a sample rat task, our approach revealed ongoing learning for more than 100 days after the saturation of success rates. Moreover, we showed that many neurons in the insular cortex of rats track the instantaneous task engagement of the rats with a resolution of a few minutes. Due to its generic formulation in reinforcement learning terminology, our work is directly applicable to the majority of animal tasks in use today.

neuroscience↗

Task-related activity in auditory cortex enhances sound representation

In auditory-guided tasks, sound presentations often occupy a small fraction of the total task time. We studied here neuronal dynamics that spanned trial duration. Many neurons had large, slow, firing rate modulations, which were not driven by sounds, were larger than the sound evoked responses, and were locked to specific time points during the task, similar to responses of hippocampal time-sensitive neurons. Concurrently, responses to sounds differed between active behavior and passive listening conditions: in the active sessions, the on-going activity just before sound presentations was higher and the responses to target stimuli were weaker but more informative about the task-relevant sounds. We show that the slow firing rate modulations caused the increased on-going activity. Using a model, we demonstrate that higher on-going activity led to more synaptic depression of the cortico-cortical synapses, reducing the tendency to produce population spikes and resulting in weaker but more informative responses.

neuroscience↗

A Rapid Anterior Auditory Processing Stream Through the Insulo-Parietal Auditory Field in the Rat

The insular cortex is believed to be involved in a wide range of auditory functions in the mammalian brain. We studied the organization and basic response properties of auditory neurons in insular cortex and adjacent areas by recording responses to sound stimuli in anesthetized rats. Auditory neurons were present in an insulo-parietal auditory field that spans the boundary between the posterior insula, particularly in the granular insular cortex and the ventral part of the secondary somatosensory cortex. Neurons in this field had narrow tuning, were preferentially tuned to relatively low frequencies (<16 kHz), and had short response latencies. Intriguingly, some auditory units in this insulo-parietal field displayed shorter onset latencies than the minimal latency in primary auditory cortex. At the same time, these units showed weaker sensitivity to deviance than units in primary auditory cortex. These results establish the existence of a rapid information stream through the insulo-parietal cortex that may parallel the pathway through the primary and anterior auditory fields.

neuroscience↗

Significantly reduced inflammatory foreign-body-response to neuroimplants and improved recording performance in young compared to adult rats

The multicellular inflammatory encapsulation of implanted intracortical multielectrode arrays (MEA) is associated with severe deterioration of their field potentials (FP) recording performance, which thus limits the use of brain implants in basic research and clinical applications. Therefore, extensive efforts have been made to identify the conditions in which the inflammatory foreign body response (FBR) is alleviated, or to develop methods to mitigate the formation of the inflammatory barrier. Here, for the first time, we show that (1) in young rats (74{+/-}8 gr, 4 weeks old at the onset of the experiments), cortical tissue recovery following MEA implantation proceeds with ameliorated inflammatory scar as compared to adult rats (242 {+/-}18 gr, 9 weeks old at the experimental onset); (2) in contrast to adult rats in which the Colony Stimulating factor 1 Receptor (CSF1R) antagonist chow eliminated ~95% of the cortical microglia but not microglia adhering to the implant surfaces, in young rats the microglia adhering to the implant were eliminated along with the parenchymal microglia population. The removal of microglia adhering to the implant surfaces was correlated with improved recording performance by in-house fabricated Perforated Polyimide MEA Platforms (PPMP). These results support the hypothesis that microglia adhering to the surface of the electrodes, rather than the multicellular inflammatory scar, is the major underlying mechanism that deteriorates implant recording performance, and that young rats provide an advantageous model to study months-long, multisite electrophysiology in freely behaving rats.

neuroscience↗

Intravenous haloperidol and cocaine alter the distribution of T CD4+ and B lymphocytes and NKT cells in rats

Modulation of dopamine transmission evokes strong behavioral effects that can be achieved by psychoactive drugs such as haloperidol or cocaine. Cocaine non-specifically increases dopamine transmission by blocking dopamine active transporter (DAT) and evokes behavioral arousal, while haloperidol is a non-specific dopamine D2 receptor antagonist with sedative effects. Interestingly, dopamine has been found to affect immune cells in addition to its action in the central nervous system. Here we address the possible interactions between haloperidol and cocaine and their effects on both immune cells and behavior in freely moving rats. We use an intravenous model of haloperidol and binge cocaine administration to evaluate the drugs impact on the distribution of lymphocyte subsets in both the peripheral blood and the spleen. We assess the drugs behavioral effects by measuring locomotor activity. Cocaine evoked a pronounced locomotor response and stereotypic behaviors, both of which were completely blocked after pretreatment with haloperidol. The results suggest that blood lymphopenia which was induced by haloperidol and cocaine (except for NKT cells), is independent of dopaminergic activity and most likely results from the massive secretion of corticosterone. Haloperidol pretreatment prevented the cocaine-induced decrease in NKT cell numbers. On the other hand, the increased systemic dopaminergic activity after cocaine administration is a significant factor in retaining T CD4+ and B lymphocytes in the spleen. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/470229v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1275eb3org.highwire.dtl.DTLVardef@1ba7afcorg.highwire.dtl.DTLVardef@1e070b9org.highwire.dtl.DTLVardef@886bf_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

Ultrastructural analysis of neuroimplant-parenchyma interfaces uncover remarkable neuroregeneration along-with barriers that limit the implant electrophysiological functions

Despite increasing use of in-vivo multielectrode array (MEA) implants for basic research and medical applications, the critical structural interfaces formed between the implants and the brain parenchyma, remain elusive. Prevailing view assumes that formation of multicellular inflammatory encapsulating-scar around the implants (the foreign body response) degrades the implant electrophysiological functions. Using gold mushroom shaped microelectrodes (gMEs) based perforated polyimide MEA platforms (PPMPs) that in contrast to standard probes can be thin sectioned along with the interfacing parenchyma; we examined here for the first time the interfaces formed between brains parenchyma and implanted 3D vertical microelectrode platforms at the ultrastructural level. Our study demonstrates remarkable regenerative processes including neuritogenesis, axon myelination, synapse formation and capillaries regrowth in contact and around the implant. In parallel, we document that individual microglia adhere tightly and engulf the gMEs. Modeling of the formed microglia-electrode junctions suggest that this configuration suffice to account for the low and deteriorating recording qualities of in vivo MEA implants. These observations help define the anticipated hurdles to adapting the advantageous 3D in-vitro vertical-electrode technologies to in-vivo settings, and suggest that improving the recording qualities and durability of planar or 3D in-vivo electrode implants will require developing approaches to eliminate the insulating microglia junctions.

neuroscience↗

The RIFF: an automated environment for studying the neural basis of auditory-guided complex behavior

Behavior consists of the interaction between an organism and its environment, and is controlled by the brain. Brain activity varies at sub-second time scales, but behavioral measures are usually coarse (often consisting of only binary trial outcomes). To overcome this mismatch, we developed the RIFF: a programmable interactive arena for freely-moving rats with multiple feeding areas, multiple sound sources, high-resolution behavioral tracking, and simultaneous electrophysiological recordings. We describe two complex tasks implemented in the RIFF. Rats quickly learned these tasks and developed anticipatory behavior. Neurons in auditory cortex and posterior insula showed sensitivity to non-auditory parameters such as location and pose. Our combination of wireless electrophysiology and detailed behavioral documentation in a controlled environment produces insights into the cognitive capabilities and learning mechanisms of rats and opens the way to a better understanding of how brains control behavior.

neuroscience↗

Stimulus-specific adaptation to behaviorally-relevant sounds in awake rats

Stimulus-specific adaptation (SSA) is the reduction in responses to a common stimulus that does not generalize, or only partially generalizes, to other stimuli. SSA has been studied mainly with sounds that bear no behavioral meaning. We hypothesized that the acquisition of behavioral meaning by a sound should modify the amount of SSA evoked by that sound. To test this hypothesis, we used fear conditioning in rats, using two word-like stimuli, derived from the English words \"danger\" and \"safety\", as well as pure tones. One stimulus (CS+) was associated with a foot shock whereas the other stimulus (CS-) was presented without a concomitant foot shock. We recorded neural responses to the auditory stimuli using chronically implanted multi-electrode arrays, recording responses telemetrically in freely moving animals before and after conditioning. Consistent with our hypothesis, SSA changed in a way that depended on the behavioral role of the sound: the contrast between standard and deviant responses remained the same or decreased for CS+ stimuli but increased for CS- stimuli, showing that SSA is shaped by experience. In most cases the sensory responses underlying these changes in SSA increased following conditioning. Unexpectedly, the responses to CS+ word-like stimuli showed a specific, substantial decrease, which we interpret as evidence for substantial inhibitory plasticity.

neuroscience↗

The anatomical boundary of the rat claustrum

The claustrum is a subcortical nucleus that exhibits dense connectivity across the neocortex. Considerable recent progress has been made in establishing its genetic and anatomical characteristics, however a core, contentious issue that regularly presents in the literature pertains to the rostral extent of its anatomical boundary. The present study addressed this issue in the rat brain.\n\nUsing a combination of immunohistochemistry and neuronal tract tracing, we have examined the expression profiles of several genes that have previously been identified as exhibiting a differential expression profile in the claustrum relative to the surrounding cortex. The expression profiles of parvalbumin, crystallin mu (Crym), and guanine nucleotide binding protein (G protein), gamma 2 (Gng2) were assessed immunohistochemically alongside, or in combination with cortical anterograde, or retrograde tracer injections. Retrograde neuronal tracer injections into various thalamic nuclei were used to further establish the rostral border of the claustrum.\n\nExpression of all three markers delineated a nuclear boundary that extended considerably (~500 m) beyond the anterior horn of the neostriatum. Cortical retrograde and anterograde neuronal tracer injections, respectively, revealed distributions of cortically-projecting claustral neurons and cortical efferent inputs to the claustrum that overlapped with the gene marker-derived claustrum boundary. Finally, retrograde tracer injections centred in nucleus reuniens, whilst including the rhomboid, mediodorsal and centromedial nuclei, revealed that insular cortico-thalamic projections encapsulated a claustral area, with strongly diminished cell label, that corresponded to the claustrum.

neuroscience↗

Demarcating the anatomical structure of the claustrum: piecing together a new functional puddle

BackgroundA major obstacle in the understanding of the functional anatomy of the claustrum has been, and continues to be, the contradiction surrounding its anatomical boundary and, in particular, its rostral (i.e. anterior to striatum), extent. In a recent review we highlighted gene expression-based evidence from the mouse brain which lends weight to the idea that the anatomical boundary of the claustrum does in fact extend rostral to the anterior apex of the striatum. In light of this evidence, in the present study, we have examined the expression of two genes that have previously been identified as having differential expression in the mouse claustrum, with the aim of: 1, establishing the true neuroanatomical boundaries of the rat claustrum; and 2, determining the efficacy of claustral marker expression in the histological verification of claustral electrode placement following electrophysiological recordings in awake behaving rats.\n\nMethodsThe expression profiles of two genes, crystallin mu (Crym) and guanine nucleotide binding protein (G protein), gamma 2 (Gng2) were assessed immunohistochemically in five male rats (one Wistar Kyoto (WK) and four Lister hooded (LH)). Prior to histological analysis, two of the rats had undergone surgical implantation of tetrodes targeting the putative rostral claustrum.\n\nResultsIn results that are consistent with those we have previously described in the mouse brain, expression of Crym in the rat brain was highly attenuated, or absent, in the claustrum, demarcating a nuclear boundary that extended considerably beyond the anterior apex of the striatum. In concordance, enriched expression of Gng2 was found in the claustrum, again extending equivalently rostral to the anterior apex of the striatum. The expression of claustral marker genes is a highly effective tool in the verification of electrophysiological electrode placement. Electrophysiological recordings from within this Gng2 and Crym-defined boundary of the rostral claustrum support previous reports of a spatial map in the rostral claustrum.\n\nConclusionsIt is now clear that the anatomical boundary of the rat claustrum does in fact extend into more frontal regions of the brain than has previously been asserted. The importance of these findings are considered in the context of the regional specificity of claustral function, anatomical connectivity and electrophysiological properties.

neuroscience↗