organotypic-slice-cultures-for-studies-of-postnatal-neurogenesis

Organotypic Slice Cultures for Studies of Postnatal Neurogenesis

Here we describe a technique for studying hippocampal postnatal neurogenesis in the rodent brain using the organotypic slice culture technique. This ...

University of Toronto

Nitric oxide (NO) is involved in neuronal transmission by modulating neurotransmitter release in adults and in stabilizing synaptic connections in developing brains. We investigated the influence of downregulation of NO synthesis on oscillatory components of ON and OFF evoked field potentials in the rat superior colliculus. NO synthesis was decreased by inhibiting nitric oxide synthase (NOS) with an acute microinjection of N(omega)-nitro-L-arginine methyl ester (L-NAME). The study focuses on rhythmic activity by analyzing fast Fourier transform (FFT). Collicular responses were recorded in anesthetized rats, at postnatal days (PND) 13-19 and adults. This time window was chosen because it is centered on eye opening. NO downregulation resulted in a dual effect depending on age and response-type. NO synthesis inhibition decreased the magnitude of oscillations in ON responses in the youngest animals (PND13-14), whereas oscillations of frequencies higher than 20 Hz in OFF responses were increased in all age groups of developing rats. In adults NO downregulation increased oscillations in ON responses and decreased oscillations in OFF responses. L-Arginine was used to increase NOS activity and its injection produced effects opposite to those seen with L-NAME. Slow oscillatory components (7-12 Hz) were unaffected in all experiments. Our data together with results reported in the literature suggest that rhythmic patterns of activity are NO-dependent.

Influence of NO downregulation on oscillatory evoked responses in developing rat superior colliculus.

The horizontal rotatory vestibulo-ocular reflex (VOR) stabilizes gaze by moving the eyes at an angular velocity proportional to head velocity, and can accomplish this for a broad range of frequencies and amplitudes of head motion. Rotation at 5 Hz and above may be processed differently than lower frequencies by the VOR network. We recorded discharges and calculated spike densities of a small sample of vestibular neurons in alert cats during low-velocity rotation at frequencies up to 8 Hz. At high frequencies, we found both vestibular-only (V-only) and eye-movement-sensitive (EM) cells that generated asymmetric output signals. Asymmetry was primarily of the cutoff type, i.e., changes in spike density were smallest for rotation in the inhibitory direction. Most cells were identified as secondary neurons. The mean spike density was 23 sp/s, which was lower than previously reported in vestibular neurons of monkeys. A few neurons had very high sensitivities, associated with phase-locking, to rotation at high frequencies. In general, vestibular neurons carried a high-pass-filtered version of rotational signals. When synaptic inputs from the vestibular commissure were quantified, we found that the immediate change in probability of firing due to commissural vestibular input was inversely correlated with the degree of high-pass filtering. At high frequencies, increased asymmetry and phase-locking occurred in some neurons. A small number of neurons responded with increased probability of firing to both directions of rotation. Together, these observations suggest that high frequencies of rotation may be encoded differently than low frequencies by central vestibular neurons in alert animals.

Asymmetric responses to rotation at high frequencies in central vestibular neurons of the alert cat.

The basis for the consolidation of memory is a controversial topic, particularly in the case of motor memory. One view is that motor memory is transferred, partially or completely, to a new location during the consolidation process ("systems consolidation"). We investigated this possibility in a primitive motor system, the vestibulo-ocular reflex (VOR). In the simple circuitry of the VOR, there are relatively few possible storage sites for memory. We partially blocked excitatory neurotransmission in the cerebellar cortex of cats with the glutamate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). If CNQX was injected immediately after 60 min of rotation under conditions that induced a learned decrease in the gain of the VOR, gain was returned to its baseline value. Expression of the new memory could also be disrupted by rotation in darkness, suggesting that consolidation had not taken place; however, after learning had continued for 3 d, expression of the learned change was diminished only slightly by blockade and was unaffected by rotation in darkness. Our interpretation of these results is that learning may take place initially in the cerebellar cortex and that during consolidation, motor memories are converted to a more distributed representation that includes the cerebellar cortex and another site.

The site of a motor memory shifts with consolidation.

Le gyrus dent&eacute;, partie int&eacute;grante du circuit hippocampe, est capable de produire de nouveaux neurones dans l&#39;&acirc;ge adulte, dont certains sont int&eacute;grer dans des circuits neuronaux qui participent au processus qui sous-tendent l&#39;apprentissage et la m&eacute;moire. L&#39;ac&eacute;tylcholine (Ach) est un neuromodulateur importante de l&#39;activit&eacute; synaptique dans l&#39;hippocampe, mais son action sur la plasticit&eacute; d&eacute;pendante de l&#39;activit&eacute; des neurones matures et jeunes n&#39;a pas &eacute;t&eacute; &eacute;tudi&eacute;e. En utilisant des pr&eacute;parations de tranches hippocampal standard et un test fonctionnel permettant de distinguer les populations neuronales jeunes et matures, nous avons constat&eacute; que l&#39;Ach a un effet stimulateur pr&eacute;f&eacute;rentiel sur la plasticit&eacute; synaptique &agrave; long terme des neurones matures. Cette m&eacute;thode diff&egrave;re son effet inhibiteur sur la plasticit&eacute; synaptique des neurones immatures, n&eacute; &agrave; l&#39;adulte. Cet effet diff&eacute;rentiel d&#39;Ach peut-&ecirc;tre contribuer &agrave; des diff&eacute;rences dans l&#39;apprentissage et la m&eacute;moire dans le cerveau de jeunes et moins jeunes, en particulier dans les t&acirc;ches qui sont sensibles &agrave; la neurogen&egrave;se adulte.

Effets biphasiques de l&#39;agoniste cholinergique carbachol sur la potentialisation &agrave; long terme dans le gyrus dent&eacute; de l&#39;hippocampe chez les mammif&egrave;res.

Der Gyrus dentatus, fester Bestandteil der hippocampal Rennstrecke ist geeignet zur Herstellung neuer Nervenzellen im Erwachsenenalter, von denen einige in neuronale Schaltkreise, die bei Prozessen zugrunde liegen integriert, lernen und Ged&auml;chtnis beteiligt. Acetylcholin (Ach) ist eine wichtige oder Neuromodulatoren synaptische Aktivit&auml;t des Hippocampus, aber seine Wirkung auf leistungsabh&auml;ngige Plastizit&auml;t von Reife und junge Neuronen wurde nicht untersucht. Mit Norm hippocampal Segment Vorbereitungen und eine funktionelle Assay f&uuml;r junge und Reife neuronale Populationen zu unterscheiden, fanden wir, dass Ach eine bevorrechtigte stimulierende Wirkung auf langfristige synaptische Plastizit&auml;t der Reife Neuronen. Dies steht im Gegensatz zu seine hemmende Wirkung auf synaptische Plastizit&auml;t unreif, Erwachsenen-US-amerikanischer Neuronen. Diese differentielle Wirkung von Ach kann beitragen, Unterschiede im lernen und Ged&auml;chtnis im Gehirn jung und alt, insbesondere bei Aufgaben, die auf der adulten Neurogenese reagieren.

Biphasische Auswirkungen die cholinerge Agonisten Carbachol auf langfristige Erm&ouml;glichung in den Gyrus dentatus des S&auml;ugetier-Hippocampus.

&#x6D77;&#x9A6C;&#xFF0C;&#x6D77;&#x9A6C;&#x4E2D;&#x7684;&#x4E00;&#x4E2A;&#x7EC4;&#x6210;&#x90E8;&#x5206;&#x662F;&#x7535;&#x8DEF;&#x7684;&#x80FD;&#x591F;&#x5728;&#x6210;&#x5E74;&#x65F6;&#xFF0C;&#x5176;&#x4E2D;&#x4E00;&#x4E9B;&#x6210;&#x4E3A;&#x96C6;&#x6210;&#x5230;&#x53C2;&#x4E0E;&#x5B66;&#x4E60;&#x548C;&#x8BB0;&#x5FC6;&#x7684;&#x57FA;&#x672C;&#x8FC7;&#x7A0B;&#x7684;&#x795E;&#x7ECF;&#x5143;&#x7535;&#x8DEF;&#x751F;&#x6210;&#x65B0;&#x7684;&#x795E;&#x7ECF;&#x5143;&#x3002;&#x4E59;&#x9170;&#x80C6;&#x78B1; &#xFF08;Ach&#xFF09; &#x662F;&#x6D77;&#x9A6C;&#x7A81;&#x89E6;&#x6D3B;&#x52A8;&#x91CD;&#x8981; neuromodulator &#x4F46;&#x5C1A;&#x672A;&#x7814;&#x7A76;&#x6210;&#x719F;&#x548C;&#x5E74;&#x8F7B;&#x7684;&#x795E;&#x7ECF;&#x5143;&#x53EF;&#x5851;&#x6027;&#x6D3B;&#x6027;&#x4F9D;&#x8D56;&#x5176;&#x884C;&#x52A8;&#x3002;&#x4F7F;&#x7528;&#x6807;&#x51C6;&#x7684;&#x6D77;&#x9A6C;&#x8111;&#x7247;&#x7684;&#x7B79;&#x5907;&#x5DE5;&#x4F5C;&#x548C;&#x529F;&#x80FD;&#x6D4B;&#x5B9A;&#x9274;&#x522B;&#x5E74;&#x8F7B;&#x548C;&#x6210;&#x719F;&#x7684;&#x795E;&#x7ECF;&#x5143;&#x4EBA;&#x53E3;&#xFF0C;&#x6211;&#x4EEC;&#x53D1;&#x73B0; Ach &#x5DF2;&#x4F18;&#x60E0;&#x7684;&#x523A;&#x6FC0;&#x4F5C;&#x7528;&#xFF0C;&#x5BF9;&#x957F;&#x671F;&#x6210;&#x719F;&#x7684;&#x795E;&#x7ECF;&#x5143;&#x7A81;&#x89E6;&#x53EF;&#x5851;&#x6027;&#x3002;&#x8FD9;&#x662F;&#x76F8;&#x5BF9;&#x4E8E;&#x5176;&#x4E0A;&#x7684;&#x4E0D;&#x6210;&#x719F;&#x3001; &#x51FA;&#x751F;&#x4E8E;&#x6210;&#x4EBA;&#x7684;&#x795E;&#x7ECF;&#x5143;&#x7A81;&#x89E6;&#x53EF;&#x5851;&#x6027;&#x7684;&#x6291;&#x5236;&#x4F5C;&#x7528;&#x3002;&#x8FD9;&#x79CD;&#x5DEE;&#x5F02;&#x5F71;&#x54CD; Ach &#x53EF;&#x80FD;&#x6709;&#x52A9;&#x4E8E;&#x5B66;&#x4E60;&#x7684;&#x5DEE;&#x5F02;&#x548C;&#x8BB0;&#x5FC6;&#x7684;&#x9752;&#x5E74;&#x4EBA;&#x548C;&#x8001;&#x5E74;&#x4EBA;&#x7684;&#x5927;&#x8111;&#xFF0C;&#x5C24;&#x5176;&#x662F;&#x5728;&#x5BF9;&#x6210;&#x4EBA;&#x795E;&#x7ECF;&#x654F;&#x611F;&#x7684;&#x4EFB;&#x52A1;&#x3002;

&#x53CC;&#x76F8;&#x5F71;&#x54CD;&#x7684;&#x80C6;&#x78B1;&#x80FD;&#x6FC0;&#x52A8;&#x5242;&#x80C6;&#x78B1;&#x7684;&#x54FA;&#x4E73;&#x52A8;&#x7269;&#x6D77;&#x9A6C;&#x9F7F;&#x72B6;&#x56DE;&#x957F;&#x65F6;&#x7A0B;&#x3002;

The dentate gyrus, an integral part of the hippocampal circuit, is capable of producing new neurons in adulthood, some of which become integrated into neuronal circuits that participate in processes underlying learning and memory. Acetylcholine (Ach) is an important neuromodulator of synaptic activity in the hippocampus but its action on activity-dependent plasticity of mature and young neurons has not been studied. Using standard hippocampal slice preparations and a functional assay for distinguishing young and mature neuronal populations, we found that Ach has a preferential stimulatory effect on long-term synaptic plasticity of mature neurons. This is in contrast to its inhibitory effect on synaptic plasticity of immature, adult-born neurons. This differential effect of Ach may contribute to differences in learning and memory in young and old brains, particularly in tasks that are sensitive to adult neurogenesis.

Biphasic effects of the cholinergic agonist carbachol on long-term potentiation in the dentate gyrus of the mammalian hippocampus.

Il giro dentato, parte integrante del circuito ippocampale, &egrave; in grado di produrre nuovi neuroni in et&agrave; adulta, alcune delle quali diventano integrati in circuiti neuronali che partecipano a processi sottostanti l&#39;apprendimento e la memoria. Acetilcolina (Ach) &egrave; un Neuromodulatore importante dell&#39;attivit&agrave; sinaptica nell&#39;ippocampo ma la sua azione sull&#39;attivit&agrave;-dipendente plasticit&agrave; dei neuroni maturi e giovani non &egrave; stata studiata. Utilizzando preparazioni standard fetta dell&#39;ippocampo e un test funzionale per distinguere le popolazioni neuronali mature e giovani, abbiamo trovato che l&#39;Ach ha un effetto stimolante preferenziale sulla plasticit&agrave; sinaptica a lungo termine dei neuroni maturi. Questo &egrave; in contrasto con il suo effetto inibitorio sulla plasticit&agrave; sinaptica dei neuroni immaturi, nato adulto. Questo effetto differenziale di Ach possa contribuire a differenze nell&#39;apprendimento e memoria nel cervello di giovani e vecchi, particolarmente in attivit&agrave; che sono sensibili alla neurogenesi adulta.

Effetti bifasico del Carbacolo agonista colinergico sul potenziamento a lungo termine nel giro dentato dell&#39;ippocampo dei mammiferi.

&#x6B6F;&#x72B6;&#x56DE;&#x3001;&#x6D77;&#x99AC;&#x795E;&#x7D4C;&#x56DE;&#x8DEF;&#x306E;&#x4E0D;&#x53EF;&#x6B20;&#x306A;&#x90E8;&#x5206;&#x306F;&#x3001;&#x3044;&#x304F;&#x3064;&#x304B;&#x306E;&#x8A18;&#x61B6;&#x30FB;&#x5B66;&#x7FD2;&#x306E;&#x57FA;&#x790E;&#x3068;&#x306A;&#x308B;&#x30D7;&#x30ED;&#x30BB;&#x30B9;&#x306B;&#x53C2;&#x52A0;&#x3059;&#x308B;&#x795E;&#x7D4C;&#x56DE;&#x8DEF;&#x306B;&#x7D71;&#x5408;&#x306B;&#x306A;&#x308B;&#x5927;&#x4EBA;&#x306B;&#x306A;&#x3063;&#x3066;&#x65B0;&#x3057;&#x3044;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306E;&#x751F;&#x7523;&#x304C;&#x53EF;&#x80FD;&#x3067;&#x3059;&#x3002;&#x30A2;&#x30BB;&#x30C1;&#x30EB;&#x30B3;&#x30EA;&#x30F3; (Ach)&#x3001;&#x91CD;&#x8981;&#x306A;&#x795E;&#x7D4C;&#x8ABF;&#x7BC0;&#x7269;&#x8CEA;&#x306E;&#x6D77;&#x99AC;&#x306E;&#x30B7;&#x30CA;&#x30D7;&#x30B9;&#x6D3B;&#x6027;&#x306E;&#x3067;&#x3059;&#x304C;&#x3001;&#x6D3B;&#x52D5;&#x306B;&#x4F9D;&#x5B58;&#x3057;&#x305F;&#x53EF;&#x5851;&#x6027;&#x3067;&#x305D;&#x306E;&#x30A2;&#x30AF;&#x30B7;&#x30E7;&#x30F3;&#x306E;&#x6210;&#x719F;&#x3068;&#x82E5;&#x3044;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x3092;&#x691C;&#x8A0E;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x305B;&#x3093;&#x3002;&#x6A19;&#x6E96;&#x306E;&#x6D77;&#x99AC;&#x30B9;&#x30E9;&#x30A4;&#x30B9;&#x6A19;&#x672C;&#x3068;&#x6A5F;&#x80FD;&#x30A2;&#x30C3;&#x30BB;&#x30A4;&#x82E5;&#x3044;&#x3001;&#x6210;&#x719F;&#x3057;&#x305F;&#x795E;&#x7D4C;&#x7D30;&#x80DE;&#x7FA4;&#x3092;&#x533A;&#x5225;&#x3059;&#x308B;&#x305F;&#x3081;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x3001;Ach &#x6210;&#x719F;&#x3057;&#x305F;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306E;&#x9577;&#x671F;&#x30B7;&#x30CA;&#x30D7;&#x30B9;&#x53EF;&#x5851;&#x6027;&#x512A;&#x9047;&#x4FC3;&#x9032;&#x52B9;&#x679C;&#x3092;&#x5F97;&#x305F;. &#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x306F;&#x3001;&#x672A;&#x719F;&#x306A;&#x5927;&#x4EBA;&#x751F;&#x307E;&#x308C;&#x3066;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306E;&#x30B7;&#x30CA;&#x30D7;&#x30B9;&#x53EF;&#x5851;&#x6027;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x305D;&#x306E;&#x963B;&#x5BB3;&#x4F5C;&#x7528;&#x306F;&#x5BFE;&#x7167;&#x7684;&#x3067;&#x3059;&#x3002;&#x3053;&#x306E;&#x5DEE;&#x52D5;&#x52B9;&#x679C; Ach &#x306E;&#x5B66;&#x7FD2;&#x306E;&#x9055;&#x3044;&#x3068;&#x7279;&#x306B;&#x6210;&#x4F53;&#x306B;&#x654F;&#x611F;&#x3067;&#x3042;&#x308B;&#x30BF;&#x30B9;&#x30AF;&#x3067;&#x8001;&#x82E5;&#x7537;&#x5973;&#x306E;&#x982D;&#x8133;&#x306E;&#x30E1;&#x30E2;&#x30EA;&#x306B;&#x8CA2;&#x732E;&#x3059;&#x308B;&#x304B;&#x3082;&#x3057;&#x308C;&#x306A;&#x3044;&#x3002;

&#x54FA;&#x4E73;&#x985E;&#x306E;&#x6D77;&#x99AC;&#x6B6F;&#x72B6;&#x56DE;&#x306E;&#x9577;&#x671F;&#x5897;&#x5F37;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x30B3;&#x30EA;&#x30F3;&#x4F5C;&#x52D5;&#x6027;&#x30A2;&#x30B4;&#x30CB;&#x30B9;&#x30C8; &#x30AB;&#x30EB;&#x30D0;&#x30B3;&#x30FC;&#x30EB;&#x306E;&#x4E8C;&#x76F8;&#x6027;&#x52B9;&#x679C;&#x3002;

&#xAC00; &#xC774;&#xB791; hippocampal &#xD68C;&#xB85C;&#xC758; &#xBD88;&#xAC00;&#xBD84;&#xC758; &#xC77C;&#xBD80;&#xB294; &#xC131;&#xC778;, &#xD559;&#xC2B5; &#xBC0F; &#xBA54;&#xBAA8;&#xB9AC; &#xAE30;&#xBCF8; &#xD504;&#xB85C;&#xC138;&#xC2A4;&#xC5D0; &#xCC38;&#xC5EC; &#xD558;&#xB294; &#xC2E0;&#xACBD; &#xD68C;&#xB85C;&#xC5D0; &#xD1B5;&#xD569; &#xB418;&#xB294; &#xC77C;&#xBD80;&#xC5D0;&#xC11C; &#xC0C8;&#xB85C;&#xC6B4; &#xC2E0;&#xACBD; &#xC138;&#xD3EC;&#xB97C; &#xC0DD;&#xC0B0; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC544; &#xC138; &#xD2F8; &#xCF5C;&#xB9B0; (Ach) &#xD574; &#xB9C8; &#xC2DC; &#xB0C5; &#xC2A4; &#xD65C;&#xB3D9;&#xC758; &#xC911;&#xC694; &#xD55C; neuromodulator &#xD558;&#xC9C0;&#xB9CC; &#xC131;&#xC219; &#xD558; &#xACE0; &#xC80A;&#xC740; &#xB274;&#xB7F0;&#xC758; &#xD65C;&#xB3D9;&#xC5D0; &#xB530;&#xB77C; &#xB2E4;&#xB985;&#xB2C8;&#xB2E4;&#xAC00; &#xC18C;&#xC131;&#xC5D0; &#xBBF8;&#xCE58;&#xB294; &#xC791;&#xC6A9; &#xC5F0;&#xAD6C; &#xB418;&#xC9C0; &#xC54A;&#xC558;&#xC2B5;&#xB2C8;&#xB2E4;. &#xD45C;&#xC900; hippocampal &#xC2AC;&#xB77C;&#xC774;&#xC2A4; &#xC900;&#xBE44;&#xC640; &#xAE30;&#xB2A5; &#xBD84;&#xC11D; &#xACB0;&#xACFC; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xC80A;&#xACE0; &#xC131;&#xC219;&#xD55C; &#xC2E0;&#xACBD; &#xC778;&#xAD6C;&#xB97C; &#xAD6C;&#xBCC4;&#xC744; &#xC704;&#xD55C;, &#xC6B0;&#xB9AC;&#xB294; Ach &#xC131;&#xC219;&#xD55C; &#xC2E0;&#xACBD; &#xC138;&#xD3EC; &#xC7A5;&#xAE30; &#xC2DC; &#xB0C5; &#xC2A4;&#xAC00; &#xC18C;&#xC131;&#xC5D0; &#xD2B9;&#xD61C; stimulatory &#xD6A8;&#xACFC; &#xBC1C;&#xACAC;. &#xC774; &#xBBF8; &#xC131;&#xC219;&#xD55C;, &#xC131;&#xC778; &#xC120;&#xCC9C;&#xC801;&#xC778; &#xC2E0;&#xACBD; &#xC138;&#xD3EC;&#xC758; &#xC2DC; &#xB0C5; &#xC2A4;&#xAC00; &#xC18C;&#xC131;&#xC5D0;&#xC758; &#xC5B5;&#xC81C; &#xD6A8;&#xACFC; &#xBE44;&#xAD50;. Ach&#xC758; &#xCC28;&#xB4F1;&#xC774; &#xD6A8;&#xACFC; &#xD559;&#xC2B5;&#xC758; &#xCC28;&#xC774; &#xBC0F; &#xC131;&#xCCB4;&#xC5D0; &#xBBFC;&#xAC10;&#xD55C; &#xC791;&#xC5C5;&#xC5D0; &#xD2B9;&#xD788; &#xC80A;&#xC740;&#xC774; &#xB178;&#xC778; &#xB450;&#xB1CC;&#xC5D0; &#xBA54;&#xBAA8;&#xB9AC;&#xC5D0; &#xAE30;&#xC5EC;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xD3EC;&#xC720;&#xB958; &#xD574; &#xB9C8;&#xAC00; &#xB1CC;&#xC5D0;&#xC11C; &#xC7A5;&#xAE30; potentiation &#xB098;&#xC544;&#xC84C;&#xB2E4; cholinergic &#xAE38; &#xD56D; &#xC81C; carbachol&#xC758; &#xD6A8;&#xACFC;.

El giro dentado, integrante del circuito hipocampo, es capaz de producir nuevas neuronas en la edad adulta, algunas de las cuales integrarse en circuitos neuronales que participan en los procesos de aprendizaje y la memoria. La acetilcolina (Ach) es un neuromodulador importante de actividad sin&aacute;ptica en el hipocampo, pero no se ha estudiado su acci&oacute;n sobre la plasticidad dependiente de la actividad de las neuronas maduras y j&oacute;venes. Usando preparaciones rebanada hippocampal est&aacute;ndar y un an&aacute;lisis funcional para distinguir poblaciones neuronales jovenes y maduras, encontramos que la Ach tiene un efecto estimulante preferencial en la plasticidad sin&aacute;ptica a largo plazo de neuronas maduras. Esto est&aacute; en contraste con su efecto inhibitorio sobre la plasticidad sin&aacute;ptica de las neuronas inmaduras, nacido en adulto. Este efecto diferencial de Ach puede contribuir a las diferencias en el aprendizaje y la memoria en el cerebro de j&oacute;venes y adultos, especialmente en tareas que son sensibles a la neurog&eacute;nesis adulta.

Bif&aacute;sico efectos de los agonistas colin&eacute;rgicos Carbacol sobre potenciaci&oacute;n a largo plazo en el giro dentado del hipocampo mam&iacute;fero.

Hippocampal neurogenesis persists in adult mammals, but its rate declines dramatically with age. Evidence indicates that experimentally-reduced levels of neurogenesis (e.g., by irradiation) in young rats has profound influence on cognition as determined by learning and memory tests. In the present study we asked whether in middle-aged, 10- to 13-months-old rats, cell production can be restored toward the level present in young rats. To manipulate neurogenesis we induced bilateral carotid occlusion with hypotension. This procedure is known to increase neurogenesis in young rats, presumably in a compensatory manner, but until now, has never been tested in aging rats. Cell production was measured at 10, 35, and 90 days after ischemia. The results indicate that neuronal proliferation and differentiation can be transiently restored in middle-aged rats. Furthermore, the effects are more pronounced in the dorsal as opposed to ventral hippocampus thus restoring the dorso-ventral gradient seen in younger rats. Our results support previous findings showing that some of the essential features of the age-dependent decline in neurogenesis are reversible. Thus, it may be possible to manipulate neurogenesis and improve learning and memory in old age.

Enhanced post-ischemic neurogenesis in aging rats.

Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age.

Yao Fang Tan

Department of Physiology

University of Toronto

Organotypic Slice Cultures for Studies of Postnatal Neurogenesis