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New Technique Images Brain Circuits, Providing Insights into Learning, Memory Pathway

By MedImaging staff writers
Posted on 25 Feb 2008
Researchers have reported that they have created a way to see, for the first time, the effect of blocking and unblocking a single neural circuit in a living animal. This groundbreaking technology allowed investigators to see how bypassing a major memory-forming circuit in the brain affected learning and memory in mice.

"Our data strongly suggest that the hippocampal neural pathway called the tri-synaptic pathway, or TSP, plays a crucial role in quickly forming memories when encountering new events and episodes in day-to-day life,” remarked Dr. Susumu Tonegawa, a professor of biology and neuroscience at Massachusetts Institute of Technology (MIT; Cambridge, MA, USA). "Our results indicate that the decline of these abilities, such as that which accompanies neurodegenerative diseases and normal aging in humans, is likely to be due, at least in part, to the malfunctioning of this circuit.”

Combining several cutting-edge genetic engineering techniques, Dr. Tonegawa's laboratory at the MIT Picower Institute for Learning and Memory devised a method called doxycycline-inhibited circuit exocytosis-knockdown (DICE-K). DICE-K allows researchers for the first time to induce and reverse a blockade of synaptic transmission in specific neural circuits in the hippocampus.

"The brain is the most complex machine ever assembled on this planet,” Dr. Tonegawa said. "Our cognitive abilities and behaviors are based on tens of thousands of molecules that compose several billion neurons, as well as how those neurons are connected. One effective way to understand how this immensely complex cellular network works in a major form of cognition like memory is to intervene in the specific neural circuit suspected to be involved.”

The hippocampus, a seahorse-shaped brain region, plays a role in memory and spatial navigation. In Alzheimer's disease, the hippocampus is one of the first areas to suffer damage; memory problems and disorientation are among the disease's first symptoms.
The hippocampus is made up of several regions--CA1, CA3, and the dentate gyrus--that are wired with distinct pathways.

The MIT study sought to determine how the interactions between neural pathways and the hippocampal regions affect learning and memory tasks. Imagine that the three hippocampal regions are computers, and neural pathways are the conduits through which the computers get data from all over the brain. The computers perform different tasks, so the types of data processing will depend on which conduits the data travels through.

The hippocampus has two major, parallel information-carrying routes: the tri-synaptic pathway (TSP) and the shorter monosynaptic pathway (MSP). The TSP includes data processing from all three hippocampal regions, whereas the MSP skips through most of them.

Utilizing DICE-K, the researchers were stunned to find that mice in which the major TSP pathway was inactivated could still learn to navigate a maze. The shorter MSP pathway was sufficient for the job. However, the maze is a task that is slowly learned over many repeated trials. When the mice were tested with a different task in a new environment that required rapid learning and memory formation, the researchers discovered that the mice with TSP shut down could not perform the task. Therefore, the TSP pathway is required for mice to rapidly acquire memories in a new environment.

"This kind of learning results in the most sophisticated form of memory that makes animals more intelligent and is known to decline with age,” Dr. Tonegawa said.

The researchers published their findings in report in the January 24, 2008, online issue of the journal Science.


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92 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (148.05793762207): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
105 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
106 (82.015991210938): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=272470000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (71.048736572266): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=272470000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (112.05673217773): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
109 (71.048736572266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
110 (72.956085205078): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=272470000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (738.85917663574): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=272470000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (685.9302520752): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (486.13548278809): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (120.16296386719): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
115 (121.11663818359): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
116 (91.075897216797): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
117 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
118 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
119 (40.054321289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
120 (69.856643676758): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
121 (53.882598876953): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
122 (416.04042053223): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 39347.887039185): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (!!!!! 3597.9747772217): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=272470000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=272470000 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 52031.993865967): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (153.0647277832): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (587.94021606445): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (64.849853515625): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (276.08871459961): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (36.001205444336): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (245.80955505371): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (37.908554077148): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (222.92137145996): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (127.79235839844): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (489.95018005371): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (357.15103149414): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (179.05235290527): SELECT name FROM jos_deeppockets WHERE id=212
138 (35.04753112793): SELECT name FROM jos_deeppockets WHERE id=212
139 (602.00691223145): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (536.91864013672): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (174.99923706055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
142 (138.99803161621): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
143 (!!!!! 22089.004516602): TRUNCATE TABLE jos_trademed_module
144 (249.86267089844): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=272470000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (!!!!! 2784.9674224854): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=272470000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (499.96376037598): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (94.175338745117): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
149 (66.995620727539): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
150 (!!!!! 1627.9220581055): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (185.01281738281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
152 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
153 (67.949295043945): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=272470000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=272470000 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (51.021575927734): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
155 (41.961669921875): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
156 (36.001205444336): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (!!!!! 1030.9219360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
158 (131.13021850586): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=272470000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=272470000 AND published='1' LIMIT 1
159 (!!!!! 1296.9970703125): select jos_twitters.link from jos_twitters where cat=10
160 (247.95532226562): select jos_facebook.link from jos_facebook where cat=10
161 (40.054321289062): select jos_google_plus.link from jos_google_plus where cat=10
162 (93.936920166016): select jos_linkedin.link from jos_linkedin where cat=10
163 (899.07646179199): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (!!!!! 1432.8956604004): insert into jos_banners_delta values (14615,'2025-07-01 01:07:38','216.73.216.249','view'),(14202,'2025-07-01 01:07:38','216.73.216.249','view'),(14203,'2025-07-01 01:07:38','216.73.216.249','view')