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Basal Ganglia — tài liệu 4 trang từ thư viện sách tennis.

Tóm tắt nội dung (trích từ tài liệu gốc): Current Biology Dispatches 2. Mayberg, H.S., Lozano, A.M., Voon, V., 7. Drysdale, A.T., Grosenick, L., Downar, J., 14. Cheng, W., Rolls, E.T., Qiu, J., Liu, W., Tang, McNeely, H.E., Seminowicz, D., Hamani, C., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, Y., Huang, C.C., Wang, X., Zhang, J., Lin, W., Schwalb, J.M., and Kennedy, S.H. (2005). R.N., Zebley, B., Oathes, D.J., Etkin, A., et al. Zheng, L., et al. (2016). Medial reward and Deep brain stimulation for treatment-resistant (2017). Resting-state connectivity biomarkers lateral non-reward orbitofrontal cortex circuits depression. Neuron 45,

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                                                                                                              Dispatches



2. Mayberg, H.S., Lozano, A.M., Voon, V.,              7. Drysdale, A.T., Grosenick, L., Downar, J.,          14. Cheng, W., Rolls, E.T., Qiu, J., Liu, W., Tang,

   McNeely, H.E., Seminowicz, D., Hamani, C.,              Dunlop, K., Mansouri, F., Meng, Y., Fetcho,             Y., Huang, C.C., Wang, X., Zhang, J., Lin, W.,

   Schwalb, J.M., and Kennedy, S.H. (2005).                R.N., Zebley, B., Oathes, D.J., Etkin, A., et al.       Zheng, L., et al. (2016). Medial reward and

   Deep brain stimulation for treatment-resistant          (2017). Resting-state connectivity biomarkers           lateral non-reward orbitofrontal cortex circuits

   depression. Neuron 45, 651�660.                         define neurophysiological subtypes of                   change in opposite directions in depression.

                                                           depression. Nat. Med. 23, 28�38.                        Brain 139, 3296�3309.

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   Catala� , M.D. (1996). Rapid-rate transcranial      8. Kringelbach, M.L. (2005). The human                 15. Nauczyciel, C., Le Jeune, F., Naudet, F.,

   magnetic stimulation of left dorsolateral               orbitofrontal cortex: linking reward to hedonic         Douabin, S., Esquevin, A., Verin, M., Dondaine,

   prefrontal cortex in drug-resistant depression.         experience. Nat. Rev. Neurosci. 6, 691�702.             T., Robert, G., Drapier, D., and Millet, B. (2014).

   Lancet 348, 233�237.                                                                                            Repetitive transcranial magnetic stimulation

                                                       9. Grabenhorst, F., and Rolls, E.T. (2011). Value,          over the orbitofrontal cortex for obsessive-

4. Greicius, M.D., Flores, B.H., Menon, V.,                pleasure and choice in the ventral prefrontal           compulsive disorder: a double-blind,

   Glover, G.H., Solvason, H.B., Kenna, H., Reiss,         cortex. Trends Cogn. Sci. 15, 56�67.                    crossover study. Transl. Psych. 9, e436.

   A.L., and Schatzberg, A.F. (2007). Resting-

   state functional connectivity in major             10. Stalnaker, T.A., Cooch, N.K., and Schoenbaum,       16. Fettes, P., Peters, S., Giacobbe, P.,

   depression: abnormally increased                        G. (2015). What the orbitofrontal cortex does not       Blumberger, D.M., and Downar, J. (2017).

   contributions from subgenual cingulate cortex           do. Nat. Neurosci. 18, 620�627.                         Neural correlates of successful orbitofrontal

   and thalamus. Biol. Psych. 62, 429�437.                                                                         1 Hz rTMS following unsuccessful dorsolateral

                                                      11. Rolls, E.T. (2016). A non-reward attractor               and dorsomedial prefrontal rTMS in major

5. Sheline, Y.I., Price, J.L., Yan, Z., and Mintun,        theory of depression. Neurosci. Biobehav.               depression: A case report. Brain Stimul. 10,

   M.A. (2010). Resting-state functional MRI in            Rev. 68, 47�58.                                         165�167.

   depression unmasks increased connectivity

   between networks via the dorsal nexus. Proc.       12. Small, D.M., Zatorre, R.J., Dagher, A., Evans,      17. Feffer, K., Fettes, P., Giacobbe, P., Daskalakis,

   Natl. Acad. Sci. USA 107, 11020�11025.                  A.C., and Jones-Gotman, M. (2001). Changes              Z.J., Blumberger, D.M., and Downar, J. (2018).

                                                           in brain activity related to eating chocolate:          1Hz rTMS of the right orbitofrontal cortex for

6. Bakker, N., Shahab, S., Giacobbe, P.,                   from pleasure to aversion. Brain 124,                   major depression: Safety, tolerability and

   Blumberger, D.M., Daskalakis, Z.J., Kennedy,            1720�1733.                                              clinical outcomes. Eur.

   S.H., and Downar, J. (2015). rTMS of the                                                                        Neuropsychopharmacol. 28, 109�117.

   dorsomedial prefrontal cortex for major            13. Johnstone, T., van Reekum, C.M., Urry, H.L.,

   depression: safety, tolerability, effectiveness,        Kalin, N.H., and Davidson, R.J. (2007). Failure    18. Hutt, A., Griffiths, J.D., Herrmann, C.S., and

   and outcome predictors for 10 Hz versus                 to regulate: counterproductive recruitment of           Lefebvre, J. (2018). Effect of stimulation

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Basal Ganglia: Striosomes and the Link between

Motivation and Action



Richard Courtemanche* and Amanda Cammalleri

FRQS Groupe de Recherche en Neurobiologie Comportementale (CSBN), and Department of Health, Kinesiology & Applied Physiology,

Concordia University, Montreal (Qc), H4B 1R6, Canada

*Correspondence: richard.courtemanche@concordia.ca

https://doi.org/10.1016/j.cub.2018.11.051



The basal ganglia integrate motivation and action across their circuits; neurons in anatomical modules called

striosomes could contribute strongly to this merger. A new method focusing on network interconnections will

allow a better understanding of the functional role of striosomes.



Motivation plays an important role in our             major role in shaping behavioral actions:               cheese, this compartment shows a

daily actions. For example in sports, let's           every day we make motivated decisions                   distinct scattered anatomical pattern

say you're about to serve for a key point in          that begin with cognition and end with                  (Figure 1B). While striosomes have been

a tennis match: you really want to get that           action. The brain's basal ganglia are an                well characterized anatomically in many

first serve in. Motivation and action                 important nexus for this motivation/action              species, data concerning their

circuits in the brain will need to quickly            interface.                                              electrophysiology and functionality have

interact. On a longer timescale, say you                                                                      been elusive. In the non-human primate,

must decide if you're going to exercise                  The input structure of the basal ganglia,            where much knowledge of the cognition/

your right on election day -- you are, and            the striatum, contains neurons that                     action interface has been explored at the

you will make sure to give your support to            receive information about both motivation               neuronal level, the scattering of

your best candidate. Both these                       and action, located in a compartment                    striosomes and their depth in the brain

examples show that motivation plays a                 called striosomes. Distributed sinuously                present a localization challenge (see

                                                      across the striatum like spaces in swiss



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Figure 1B). A new study by Hong et al. [1],    A                                         B Stimulate

reported recently in Current Biology,

delivers important new insight into            C  Record                                 Striosomes

how neural activity from striosomes can                                                             Matrix

be localized, permitting us to address

their functionality. The authors devised                                    Str          AMFC

a novel way to determine neuronal                 LHb                                    OFC

activity corresponding to striosomal

sites in the awake behaving monkey,                       RMTg  GPi

by using an approach based on

neural interconnection patterns. This                              SNc

study opens further avenues for                           VTA

research on striatal compartments to

help better understand their role in mood                                                                                                                                                   Current Biology

and action.

                                               Figure 1. The striato-pallidal-habenular pathway and the stimulation method to identify

   On a larger scale, for optimized            striosomes.

performance, motivated actions require         A look at basal ganglia organization at various levels, outlining the (A) micro-, (B) meso- and (C) macro-

contributions from multiple interacting        levels. These span the cellular, local networks, and systems levels of the central nervous system. This

cortical brain areas, complemented by          figure also illustrates the strategy used to electrophysiologically locate striosomes, based on a

critical subcortical loops [2]. These          combination of stimulation in the striatum and recording in the lateral habenula; see the striatal inset in

interconnected loops bring together            (B). By systematically stimulating multiple locations in the striatum and recording responses in the

important calculations from the                lateral habenula, striosome locations were estimated, as their stimulation produces strong habenular

cerebellum and basal ganglia in decision,      excitatory or inhibitory responses. The pathway is presented in (C). Striosomes send inhibitory signals

planning, and execution of actions [3]. In     to the internal globus pallidus (GPi), red arrow, which, in turn, stimulate neurons in the lateral habenula,

their overall network, the basal ganglia       yellow arrow. The striatum receives cortical input from the antero-medial frontal cortex (AMFC) and

bring together the motivational and            orbitofrontal cortex (OFC). The lateral habenula sends downstream signals via the rostromedial

purpose-driven aspects of successful           tegmental nucleus (RMTg) to dopaminergic nuclei involved in reward and affect, the substantia nigra

action plans, as well as playing a critical    pars compacta (SNc) and the ventral tegmental area (VTA). The feedback connections are not

role in the formation of habits [4]. The       indicated, for clarity. The goal of the procedure was to locate, with precision, the limits of striosomes.

striatum and its compartments, the             Multiple stimulation sites were used to locate putative striosomal sites; see the schematic in (A). Panels

striosomes and the matrix (Figure 1C) are      (B) and (C) adapted from the atlas found at http://brainmaps.org (see [20]).

well-established subdivisions, largely due

to detailed anatomical work from the           striatum via a two-synapse                stimulating this pathway, Hong et al. [1]

same laboratory [5�7], with neurons being      interconnection (see the pathway          affected the balance in this disynaptic

part of striosomes or part of the matrix       representation in Figure 1C, identifying  connection.

(which is sometimes further parcellated        the striato-pallidal and pallido-

into matrisomes) [6]. The striosomes in        habenular links), while using repeated       Located near and having evolved

particular were first identified by their      stimulations to map the striatum.         alongside the pineal gland, the lateral

neurochemical properties [7], being linked     The striatal stimulations activate the    habenula serves as an important juncture

with motivational aspects via dopamine         pallido-habenular circuit, inhibiting     between the basal ganglia and limbic

neurotransmission [8,9]; a schematic           globus pallidus neurons, which in         system, and it responds to negative

rendering of striosomes is shown in            contrast send excitatory projections      events to aid in emotive decisions and

Figure 1A,B. Neurons in the matrix             to the lateral habenula [10]. By          movement in potentially threatening

compartment of the striatum combine                                                      situations [11,12]. It signals negative

information from many cortical regions

to optimize actions [6]. But due to

technical difficulties in determining

which neurons are part of striosomes

during behavioral electrophysiology [9],

much remains to be uncovered

concerning the function of striosomes.

More knowledge on the operation of

these circuits would provide important

insight on how the brain programs

motivated actions.



   To determine which parts of the

striatum consist of striosomes, Hong et al.

[1] recorded neuronal activity in the lateral

habenula, connected downstream of the



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possible outcomes to other brainstem         represented in Figure 1A. It provided           also shows strong oscillations in

neuromodulatory areas, including the         high-probability sites along the track to       response to rewarded actions [18];

ventral tegmental area, substantia nigra     be considered as part of the striosomal         also second, stimulation of small striatal

pars compacta, dorsal/medial raphe           system.                                         zones -- which could correspond to

nuclei, and laterodorsal tegmentum, by                                                       striosomes -- can elicit an anxious state

acting upon dopamine, serotonin, and            The careful and dense mapping                in a monkey, a phenomenon related to

norepinephrine receptors [12].               constitutes an important component of           beta-band oscillations [19]. These

                                             establishing the method, as the size of         elements provide evidence that

   The lateral habenula plays an important   striosomes is around 500 mm wide; by            oscillatory signals flowing through

role in decision-making by labelling         advancing in the track too quickly, some        striosomes could represent a mechanism

experiences as either aversive or            striosome sites could be missed.                of influence on the expression of mood

rewarding in comparison to expectations.     Following this mapping, a detailed              and actions.

Over-activation of the habenula can lead     quantitative analysis revealed `hotspots'

to a negative bias, and to beliefs that      along the track, which represented high-           Overall, using a finely-tuned

outcomes are worse than they really are.     probability sites for putative striosome        methodology, Hong et al. [1]

In a potentially threatening situation, the  locations. These were then compared             complemented their detailed seminal

habenula will increase its inhibitory        with the anatomical localization of             work on striosomes with an innovative

activity on dopamine neurons in the          striosomes, using classical micro-              electrophysiological approach to tease

ventral tegmental area and the substantia    anatomical methods. This last                   out the details of striatal modularity and

nigra pars compacta. Conversely, a tonic     comparison completed the elegant work           connectivity. This study paves the way for

under-activation of the habenula can do      of localization, relating the anatomical        future efforts in striosome population

the opposite, giving individuals a positive  compartment with the physiological              coding and its relation to complex

bias and beliefs that outcomes are less      signals.                                        motivated behaviours. By revealing which

negative than in reality, leading to                                                         neurons belong to striatal compartments,

increased risk-taking and disinhibited          The final step in the Hong et al. [1] study  this methodology will allow us to

behaviors [13]. Dysregulation of the         involved further characterization of the        determine the sensorimotor, cognitive

habenula has been associated with            electrophysiological responses, to better       and motivation-based neural populations

depression, sleep disorders, anxiety, and    understand the place of striosomes within       involved in behavior, and their

schizophrenia [11].                          the local and overall networks of the basal     computational interactions. Perhaps,

                                             ganglia and limbic system. Following            further along the way, we will also be able

   In their experiments, Hong et al. [1]     striosome stimulation, multi-unit activity      to determine for sure the optimal neural

used a precise combination of striatal       in the lateral habenula would present a         state -- and involved networks -- to

stimulation coupled with lateral habenula    rhythm in the beta (12�30 Hz) range. As         perfectly hit (but not over-hit!) that winning

recordings, along with detailed histologic   similar rhythmic phenomena have already         tennis serve, or to be fully engaged in the

identification. This served to determine if  been uncovered in basal ganglia circuits        electoral process.

the stimulated sites were within             (for example [14�16]), this means that the

striosomes, via the response in the          habenula could show reverberating               REFERENCES

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Human Genetics: The Evolving Story of FOXP2



Simon E. Fisher1,2,3

1Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands

2Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlandstocsum

3Twitter: @ProfSimonFisher

Correspondence: simon.fisher@mpi.nl

https://doi.org/10.1016/j.cub.2018.11.047



FOXP2 mutations cause a speech and language disorder, raising interest in potential roles of this gene in

human evolution. A new study re-evaluates genomic variation at the human FOXP2 locus but finds no

evidence of recent adaptive evolution.



One longstanding challenge in biology is               language skills, one of the most distinctive            years later, Atkinson and colleagues [6]

to understand how changes in the human                 capabilities of Homo sapiens, this gene                 perform a thorough investigation of

genome contributed to the evolution of                 was seen as an obvious candidate for                    modern human FOXP2 variation, taking

our species. With advances in molecular                evolutionary study. This led to two                     advantage of genome sequences

methods, this question can be                          independent reports in 2002, which                      available from diverse populations across

investigated by comparing DNA                          established that, despite high sequence                 the world; these new analyses provide no

sequences from Homo sapiens to those of                conservation in primates, the human                     support for recent selection, overturning

other great apes, and even to archaic                  FOXP2 protein differed from its                         prior conclusions.

hominins, such as Neandertals, as well as              chimpanzee counterpart at two amino-

by searching for signs of Darwinian                    acid sites [4,5]. Moreover, when the                       FOXP2 was originally discovered

selection in the genomic variation of living           studies examined nucleotide variation in                through intensive studies of a large family

human populations [1]. In 2001, a study                the relevant part of the genomic locus in               in which fifteen relatives, across three

reported the first case of a gene mutated              living populations, patterns were                       generations, had problems sequencing

in a developmental speech and language                 compatible with recent positive selection               the rapid co-ordinated movements that

disorder [2]. The culprit, a gene called               having acted on FOXP2 [4,5]. FOXP2                      facilitate fluent speech, accompanied by

FOXP2, attracted the attention of                      became a poster-child for genes that may                impaired language production and

researchers across multiple disciplines                have played a role in the emergence of                  comprehension [2]. All affected members

[3]. Given its link to acquisition of spoken           modern humans. Now, more than 15                        carried a heterozygous point mutation in

                                                                                                               FOXP2, disturbing the function of the



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