L46. SPATIAL NAVIGATION Rattus norvegicus What do we know about the ecology of rats? BioNB424 Cosmopolitan Nov. 16, 2011 Human settlements Rattus norvegicus Nocturnal Diet L = CA1 W= neuron Origin 1 2 Rattus belongs to Rodentia Wild Rattus live in burrows Rodentia Rodents: mice, rats, hamsters, squirrels, gophers, porcupines, beavers, etc. f n f n e e e e e f. food e n. nest e e e. entrance e e n f e e e e 4 Calhoun, 1963 J.B. Calhoun, The Ecology and Sociology of the Norway Rat. U.S. Public Health Service Publication No. 1008 , (1963). Calhoun (1963) kept rats in a semi-natural enclosure. Norway rats dug 3 underground tunnels and chambers. Rats were used in early behavioral studies Radial Arm Maze Psychology testing. David Olton Model of human behavior Easy Maze running Edward Tolman (1886-1959). (focus on behavior) Maze learning ‘cognitive map’ ‘Latent learning’ 5 6 1
Radial Arm Maze Olton Radial Arm Maze Observe path taken Typical track of rat in radial arm food reward to find food pellets, maze. at end of each depending on cues available in different arm arms of maze. 7 8 Evidence that Hippocampus is involved in Hippocampus spatial memory Human patient, H.M. (studied by Brenda Milner and surgeon William Scoville (1950’s). Brenda Milner Scoville Henry Molaison 9 10 Lesion in H.M. 1 2 3 11 12 2
Popular thriller film, MEMENTO depicts human with memory loss after hippocampal lesion (caused by bullet wound) 13 14 dentate gyrus CA3 ENTORHINAL CORTEX granule cells CA1 cells 15 16 Cajal’s circuit diagram of Hippocampal Formation Hippocampus Trisynaptic pathway: (1) fibers enter Hippocampus from perforant pathway (which originates in the entorhinal cortex) to terminate on Granule cells. 2) Mossy fiberts connect the dentate to CA3 neurons. 3) Schaffer collaterals of the CA3 connect to CA1 pyramidal cells. - Carew (2000) -Commissural connections which pass through Fimbria to synapse on CA1 cells. 17 18 3
2) Lesions to Hippocampus impairs 3) Behavior in Morris Water Maze spatial learning in rodents Rat in Morris water maze swims in cloudy water, submerged platform is hidden from view. Platform is fixed in position relative to external visual cues. mean Testing: probe trials test for swimming quadrants with no platform after correct training with platform. responses http://www.sciam.com/article.cfm?articleID=000DA854-8ACE-1CBD-B4A8809EC588EEDF&sc=I100322 19 20 Olton, 1977 (from Carew, 2000) 4) Imaging of Human Brain shows involvement of right …shows deficit after hippocampal lesion Hippocampus During Spatial Memory Tasks Human subject watching film about vehicle driving from point A to point B in Irish town. Control: film of cars moving past non-moving point in space (activity difference shown as colored area). Human taxi driver mentally recalling route around city of London. Right hippocampus activity only. From Maguire (1996). 21 Image show area of increased 22 blood flow measured by FMRI Hippocampal volume of London TaxiDrivers is slightly larger than The Rodent (Rat) Hippocampus control subjects (non-taxidriver) Elanor Maguire et al (2000) Volume of posterior hippocampus increases with time on job (as Taxidriver). 23 24 4
Rodent Hippocampus Hippocampal Formation Dentate Gyrus Carew (2000) 25 26 Place Cells in the Hippocampus Place Cells in the Hippocampus white cue card (photo) provides cue of location. Discovered in 1971 by John O’Keefe and John Dostrovsky. Recording Not odor. from single cells in hippocampus while freely --Rotate card, response field changes. moving rat move around in a closed space. Spike recordings from CA1 No change in firing pattern when lights cell. are off. the lights are off and cue card Where was the rat when is not visible. the cell fired? Rat is capable of “dead reckoning” using idoeothetic (internally-generated) cues (such as acceleration, gravity, Muller, Kubie, Ranck (1987) distance walked, etc.) 27 28 experiments of Muller, Kubie, Ranck, (1987) Properties of Place Cells Place cells are stable over time Place cells are the CA1 Pyramidal neurons that serve as the output cells for the Recording of a single place cell over a hippocampus. 19 day period. Place cells are sometimes broadly On each day indicated, the rat was responsive, sometimes focused point in placed in the same circular arena to record spikes from the same large space, sometime more than one place. pyramidal neuron (implanted electrode). Eric Hargreaves Robert Muller Lab 29 30 5
Place cells can fire in anticipation of a turn in a given maze. Properties of Place Cells Position of place cells is influenced by visual cues, and by vestibular cues. According to O’Keefe and Nadel (1978). The hippocampus, with its Rat is trained to place cells, is the site for the cognitive map (although there is no turn left, and evidence that the place cells are mapped in any way). then turn right on successive runs through maze. Prior to right turn trial, vigorous firing. prior to a left turn trial, cell fires very little From experiments of Howard Eichenbaum. 31 32 Head direction cells Synaptic plasticity in the Hippocampus Stimulation at any one of the three Navigation requires both a ‘map’ excitatory connections shows plasticity of space and a compass to tell (Bliss and Lømo, 1973) direction. Brief, high frequency burst causes increased EPSP. Can last for hours. Head direction specific cells discovered James Ranck (1984) in postsubiciculum. Long Term Potentiation (LTP). Cells fire when head is in fixed direction, both in standard and in novel environments. Stimulation of Schaffer collaterals, record 33 34 from CA1 neuron in the hippocampus. LTP Characteristics LTP mediated by NMDA type Glutamate Receptor The NMDA receptor binds to glutamate, opens a channel for Calcium ions. In the absence of cell Stimulation of just a few Specificity: Stong stimulation at one If a weak input arrives at the depolarization, fibers does not generate an site produces LTP there, but there same time as a strong input, LTP. Instead, different inputs is no LTP at a different site. The Mg ++ ions plug there will be association must cooperate to get the effect is plasticity at the post between the two. LTP will be up the NMDA effect. synaptic site. produced at the weak input. receptor, not Here, just a weak input is much of a given shocks. No LTP. response Similar stimulation of strong input gives LTP. 35 36 6
NMDA Receptor Allows Coincidence Detection in Post- NMDA: Double-Gated Synaptic Neuron When the cell is Requires synaptic transmitter (glutamate). depolarized (say, by activating a Requires simultaneous depolarization of second pathway, which may also terminal. involve a glutamate LTP: an example of a synapse that shows receptor), the Mg ++ pops out of Hebbian Learning the pore. (if a pre-synaptic fiber was active when a post synaptic cell fired, Extra Ca ++ . the synapse should be strengthened). stronger response; bigger EPSP. 37 38 LTP’s role in spatial learning can be established by Transgenic + Knockout Mice specific inhibitors of NMDA receptors Now possible to knock out a gene for a specific receptor, in a specific part of • AP5 is NMDA blocker. What is brain. the spatial learning in AP5 mice? • chronic AP5 infusion causes Combine transgenic mouse (insert new gene) with gene knockout that control failure to learn on Morris water expression in specific cell types. maze Expression of a modified NMDA receptor in CA1 neurons in mouse. • Results of water maze learning trials comparing normal to AP5 treated mice. 8 days of training, results of test trial on 9 th day. Tonegawa et al 39 40 Recording from Place Cells in Virtual Reality Environment Permits Intracellular Recording Mutant has defect in the LTP behavior in the Schaffer collateral pathway in the Hippocampus. (Input to CA1 cells) Harvey, C. D., Collman, F., Dombeck, D. A. and Tank, D. W. (2009). Intracellular dynamics of hippocampal place cells during virtual navigation. Nature 461 , 941-946. In the Morris water maze, mutant mice do not learn the position of the platform 41 42 7
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