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A low cost, high precision subminiature microdrive for extracellular unit recording in behaving animals
Journal of Neuroscience Methods 92 (1999) 87 – 90 www.elsevier.com/locate/jneumeth
A low cost, high precision subminiature microdrive for extracellular unit recording in behaving animals David K. Bilkey *, Gary M. Muir Department of Psychology, Uni6ersity of Otago, Box 56, Dunedin, New Zealand Received 3 March 1999; received in revised form 28 June 1999; accepted 30 June 1999
Abstract A new design for an inexpensive and reliable subminiature microdrive for unit recording in the freely moving animal is presented. The ‘Scribe’ microdrive is (a) of a small size and low weight, (b) allows for precise advancement of the electrodes, (c) permits stable unit recordings over time, (d) is simple to install, and (e) is economical to construct. These advantages are a result of its simple, single screw-based drive system and the ready availability of component parts. The Scribe microdrive is a small diameter device suitable for multi-site, multi-electrode applications. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Microdrive; Single-unit recording; Freely moving animals; Chronic recording; Multichannel electrode
1. Introduction A major aim of neuroscience is to understand the relationship between brain activity and behaviour. To this end, investigators have developed techniques whereby small-diameter, high impedance, microelectrodes are used to record single unit activity within the brain of awake behaving animals. These techniques usually involve attaching the electrodes to a device that allows for their gradual advancement into the brain structure of interest. Such a device (or microdrive) should meet several requirements. (a) Small size and low weight. This is obviously of benefit when the animal of interest is small (e.g. rats or mice). The use of small drives also allows for the simultaneous implantation of several microdrives into the brain, and further, decreasing the size of the drive reduces the possibility that it will be knocked and displaced during the recording process. (b) Precise advancement. For single unit recording, the drive should be able to be advanced in increments of 10–20 mm over a range of 1 – 2 mm. Additionally, a drive might also allow for electrode withdrawal in order to optimise placement or to allow for multiple penetrations. * Corresponding author. Fax: +64-3-4798335. E-mail address: [email protected] (D.K. Bilkey)
(c) Stability over time. Ideally, most unit recordings should be stable over at least 24 h. Even if the researcher is not interested in analysing activity over such long periods, if the drive is stable then the probability that a unit will be lost, or that the morphology of the recorded waveform will change as a result of electrode movement during the recording period, is decreased. (d) Simple installation. The more rapid the initial implantation procedure, the more viable the preparation is ultimately likely to be. (e) Low cost. Unfortunately, requirements (a–c) tend to preclude against low cost, as small size and precision usually requires fine tolerance machining of the component parts. It is possible to design a stable, simple and inexpensive microdrive by building a device with two or three support legs, and with the electrode attached to a chassis supported from these legs. If the legs are threaded, then it is possible to manipulate the electrode within the brain by turning these drive screws. This type of drive tends, however, to be rather large and, furthermore, may compromise recording quality because of yaw that is generated as the drive screws are turned sequentially. In contrast, a microdrive built around a single drive screw that pushes an electrode into the brain is potentially half (or less) of the width of a multiple screw design. This type of drive is, however,
0165-0270/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 5 - 0 2 7 0 ( 9 9 ) 0 0 1 0 2 - 8
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D.K. Bilkey, G.M. Muir / Journal of Neuroscience Methods 92 (1999) 87–90
usually more difficult to build (and hence more expensive) because of the requirement that the rotating motion of the drive screw is not transferred to the electrode. A failure to constrain this rotary motion causes the electrode to twist as it enters the brain, reducing the recording quality. Previous single-screw microdrive designs have eliminated this rotation by having the electrode holder keyed to a stable section of the drive so that the holder is free to move along its major axis only. This approach results, however, in an increase in the complexity of the device. Several previously described drives of this type, for instance, are composed of a relatively large number of separate components, many of which require fairly sophisticated machining (Deadwyler et al., 1979; Amos et al., 1989; Bland et al., 1990; Malpeli et al., 1992; Korshunov, 1995). We present here an alternative approach to the construction of a single screw microdrive that (a) utilises a novel method to isolate the rotation of the driving screw from the electrode assembly, (b) can be built from components that are readily available and have virtually no cost and yet are already machined to fine tolerances, and (c) that is small (22 mm tall from skull to drive screw with screw at highest position), lightweight (0.39 g) and stable.
1, component 5). The length of this barrel will depend on the amount of travel required in the microdrive (typically we utilise a barrel length of 15 mm which provides for a travel of 2 mm). A notch is filed in one end of this tube to allow the electrode wires to escape from inside the drive. The fit of the nib end of the Bic™ ball point and its nylon support cylinder (i.e. the precursor of component 2, Fig. 1) is tested inside the aluminium tube. This should be an interference fit; loose enough so that it can be pushed through the tube, but not be so loose that it will fall under its own weight if the tube is held in the upright position. In our experience, the type of ballpoint pen (e.g. medium point, fine point) used can make a difference to this fit with each type having slight variations in the diameter of the nylon sleeve. If the nylon needs to be reduced slightly in diameter to allow for this level of fit, this is easily achieved by locating the item in an electric drill and holding fine abrasive paper against it as it rotates. If the nylon is too loose within the tubing, this can be overcome by gently squeezing the tubing (with the insert inside) until an interference fit is obtained. The nylon cylinder should now be cut in half (Fig. 1a, cut c 1) on the nib side of the flange and then shortened (Fig. 1a, cut c 2) to create component 2 of
2. Material and methods The basic principle of the design is simply that a rotational torque cannot be imparted to an object (a) if the two objects are not rigidly connected and if the only point of contact between the rotating and non-rotating objects is at the axis of rotation or (b) if the rotational force generated across the contact point between the two objects is insufficient to overcome the friction that prevents the driven object from rotating. The ‘Scribe’ microdrive described in this paper takes advantage of both of these principles. As can be seen in Fig. 1a, the movement of the driving screw is transferred to the electrode assembly via a conical device (that drives at or near the axis of rotation) that has a rolling ball mechanism at the tip (that minimises friction at the contact point). Although this conical/ball device would be expensive to machine from scratch, luckily it is readily available within the nib assembly of the ubiquitous ball-point pen.
3. Construction The metal ‘ball point’ section and the nylon cylinder that this ball point sits inside are extracted from the end of a standard Bic™ ball point pen. A section of aluminium tube (2.4 mm i.d., 3.15 mm o.d.) is cut to an appropriate length so as to create an outer barrel (Fig.
Fig. 1. The Scribe microdrive and its components. (a) The ballpoint and nylon sleeve after removal from the pen. Cut c 1 is required to separate (1), the pen nib (rear section), from (2), the pen nib (front section with ballpoint). Additional cuts (at approximately the location indicated by cut c2 and c3) may be required to shorten these two components. (b) Side view of the fully assembled microdrive: (1) pen nib (rear section); (2) pen nib (front section with ballpoint); (3) guide cannula; (4) electrode wires; (5) aluminium tubing; (6) hex-head drive screw.
D.K. Bilkey, G.M. Muir / Journal of Neuroscience Methods 92 (1999) 87–90
Fig. 1a. The remaining portion of the nylon sleeve can also be shortened (Fig. 1a, cut c3) to create component 1 of Fig. 1a. Component 1 is then glued into the end of the aluminium barrel without the notch. Note that the outside of the nylon and the inside of the aluminium tubing should first be scoured to assist the adhesion of the glue to these surfaces. A thread should then be tapped through the hole in the centre of this insert and the driving screw (e.g. 1/80 in. Hex Screw, 1/2 in. length, Small Parts Inc., Miami Lakes, FL) threaded into this hole. At this stage, the electrode assembly (Fig. 1, component 3) should be mounted into the open end of the nylon cylinder that holds the metal nib (Fig. 1, component 2). Our current electrode assembly is composed of a bundle of seven or eight 25 mm microwire electrodes threaded inside a 30 gauge (hypodermic needle) guide. The tail end of the electrodes are bent backwards to lie alongside the guide before the whole electrode assembly is glued inside the nylon tube. The guide is kept parallel to the main axis of the drive during the gluing process by supporting it in a simple jig. The device is then assembled by pushing the nylon tube and metal ball point into the aluminium barrel until the ball point touches the drive screw. The electrode wires are then routed out of the drive through the notch at the end and coated with liquid rubber (Color Guard™, Permatex Industrial, Newington, CT) to prevent these chafing against the inside edge of the notch. These electrodes can then be connected to a separate headplug assembly, either affixed to the microdrive itself or free-standing. The microdrive assembly should be mounted onto the surface of the skull so that the base of the aluminium barrel is against the bone and the tip of the guide cannula is several hundred microns above the dura. At this stage, the tip of the electrodes should be through a hole created in the dura and located immediately above the brain area of interest. The whole assembly can then be fixed in place by dental cement anchored to skull screws. A small quantity of petroleum jelly should be placed around the base of the drive to prevent dental cement flowing inside the barrel area. After the animal has recovered from the surgery, recordings can be conducted and the electrode can be advanced by small turns of the drive screw. Our experience is that 1/16 of a turn ( 20 mm) increments are possible.
4. Performance We have used the Scribe microdrive to record well isolated units in both the hippocampus and perirhinal cortex regions of the brain in freely-moving animals. Good quality recordings have been made in drives that have been implanted for up to 7 months and in some
89
Fig. 2. This figure provides an example of a stable hippocampal unit recording made with the scribe drive. The unit waveform (top) and corresponding ‘place field’ (firing rate plotted across the floor of the rectangular recording chamber; bottom) recorded on (a) day 1 and (b) day 4 of an experiment. Note that the location of the place field within the recording chamber is virtually unchanged across the 3-day delay indicating that the same cell was being recorded on day 1 and 4.
cases signal-to-noise ratios of up to 7:1 have been obtained. Stable recordings of individual units have been made for periods of up to 1 month (note that this time does not necessarily reflect the maximum time that a particular unit could be maintained, it merely reflects the duration of our recording protocol). An example of a recording from a hippocampal ‘place cell’ (Muller, 1996; Muir and Bilkey, 1999) is illustrated in Fig. 2, with recordings made from this unit during a baseline period (Fig. 2a) and then after a 3-day interval (Fig. 2b). The fact that the waveform is similar across recordings (Fig. 2a (top), Fig. 2b (top)) and that the cell’s ‘place field’ is unchanged across this period (Fig. 2a (bottom), Fig. 2b (bottom)) is an indication that the same cell was being recorded in both sessions. In summary, we believe that this new microdrive is an advance over previous designs based around a single screw, primarily because of its ease of manufacture and small size (Goldberg et al., 1993). These factors make it very suitable for multiple-site, multiple-drive applications. As it is described, however, it is lacking in a feature that some other, more complex designs (Deadwyler et al., 1979; Korshunov, 1995) exhibit. That is, it does not allow for electrode withdrawal, and thus the possibility of multiple penetrations. One possible means of achieving this goal, however, would involve mounting the electrode cannula off-centre inside the drive and clamping the whole assembly as described above inside
90
D.K. Bilkey, G.M. Muir / Journal of Neuroscience Methods 92 (1999) 87–90
a guide sleeve (a piece of tubing with an internal diameter equivalent to the outer diameter of the microdrive) that would be attached to the skull. At the end of a penetration the microdrive could be withdrawn from the guide tube, rotated so as to reposition the electrode and remounted into the guide. The potential for this type of modification will be investigated in future versions of the drive.
References Amos A, Armstrong DM, Harris R, Marple-Horvat DE. A lightweight hybrid microdrive for use with awake unrestrained animals. J Neurosci Methods 1989;28:219–24. Bland BH, Colom LV, Mani TE. An improved version of a direct-
.
drive, nonrotating manual microdrive. Brain Res Bull 1990;25:441 – 3. Deadwyler SA, Biela J, Rose G, West M, Lynch G. A microdrive for use with glass or metal microelectrodes in recording from freelymoving rats. Electroencephalogr Clin Neurophysiol 1979;47:752– 4. Goldberg E, Minerbo G, Smock T. An inexpensive microdrive for chronic single-unit recording. Brain Res Bull 1993;32:321–3. Korshunov VA. Miniature microdrive for extracellular recording of neuronal activity in freely moving animals. J Neurosci Methods 1995;57:77 – 80. Malpeli JG, Weyand TG, LaClair R. A new method of mounting and directing chronically implanted microdrives. J Neurosci Methods 1992;44:19 – 26. Muir GM, Bilkey DK. Instability in the place field location of hippocampal place cells following lesions of the perirhinal cortex. Soc Neurosci Abstr 1999; in press. Muller R. A quarter of a century of place cells. Neuron 1996;7:813–22.
A low cost, high precision subminiature microdrive for extracellular unit recording in behaving animals David K. Bilkey *, Gary M. Muir Department of Psychology, Uni6ersity of Otago, Box 56, Dunedin, New Zealand Received 3 March 1999; received in revised form 28 June 1999; accepted 30 June 1999
Abstract A new design for an inexpensive and reliable subminiature microdrive for unit recording in the freely moving animal is presented. The ‘Scribe’ microdrive is (a) of a small size and low weight, (b) allows for precise advancement of the electrodes, (c) permits stable unit recordings over time, (d) is simple to install, and (e) is economical to construct. These advantages are a result of its simple, single screw-based drive system and the ready availability of component parts. The Scribe microdrive is a small diameter device suitable for multi-site, multi-electrode applications. © 1999 Elsevier Science B.V. All rights reserved. Keywords: Microdrive; Single-unit recording; Freely moving animals; Chronic recording; Multichannel electrode
1. Introduction A major aim of neuroscience is to understand the relationship between brain activity and behaviour. To this end, investigators have developed techniques whereby small-diameter, high impedance, microelectrodes are used to record single unit activity within the brain of awake behaving animals. These techniques usually involve attaching the electrodes to a device that allows for their gradual advancement into the brain structure of interest. Such a device (or microdrive) should meet several requirements. (a) Small size and low weight. This is obviously of benefit when the animal of interest is small (e.g. rats or mice). The use of small drives also allows for the simultaneous implantation of several microdrives into the brain, and further, decreasing the size of the drive reduces the possibility that it will be knocked and displaced during the recording process. (b) Precise advancement. For single unit recording, the drive should be able to be advanced in increments of 10–20 mm over a range of 1 – 2 mm. Additionally, a drive might also allow for electrode withdrawal in order to optimise placement or to allow for multiple penetrations. * Corresponding author. Fax: +64-3-4798335. E-mail address: [email protected] (D.K. Bilkey)
(c) Stability over time. Ideally, most unit recordings should be stable over at least 24 h. Even if the researcher is not interested in analysing activity over such long periods, if the drive is stable then the probability that a unit will be lost, or that the morphology of the recorded waveform will change as a result of electrode movement during the recording period, is decreased. (d) Simple installation. The more rapid the initial implantation procedure, the more viable the preparation is ultimately likely to be. (e) Low cost. Unfortunately, requirements (a–c) tend to preclude against low cost, as small size and precision usually requires fine tolerance machining of the component parts. It is possible to design a stable, simple and inexpensive microdrive by building a device with two or three support legs, and with the electrode attached to a chassis supported from these legs. If the legs are threaded, then it is possible to manipulate the electrode within the brain by turning these drive screws. This type of drive tends, however, to be rather large and, furthermore, may compromise recording quality because of yaw that is generated as the drive screws are turned sequentially. In contrast, a microdrive built around a single drive screw that pushes an electrode into the brain is potentially half (or less) of the width of a multiple screw design. This type of drive is, however,
0165-0270/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 5 - 0 2 7 0 ( 9 9 ) 0 0 1 0 2 - 8
88
D.K. Bilkey, G.M. Muir / Journal of Neuroscience Methods 92 (1999) 87–90
usually more difficult to build (and hence more expensive) because of the requirement that the rotating motion of the drive screw is not transferred to the electrode. A failure to constrain this rotary motion causes the electrode to twist as it enters the brain, reducing the recording quality. Previous single-screw microdrive designs have eliminated this rotation by having the electrode holder keyed to a stable section of the drive so that the holder is free to move along its major axis only. This approach results, however, in an increase in the complexity of the device. Several previously described drives of this type, for instance, are composed of a relatively large number of separate components, many of which require fairly sophisticated machining (Deadwyler et al., 1979; Amos et al., 1989; Bland et al., 1990; Malpeli et al., 1992; Korshunov, 1995). We present here an alternative approach to the construction of a single screw microdrive that (a) utilises a novel method to isolate the rotation of the driving screw from the electrode assembly, (b) can be built from components that are readily available and have virtually no cost and yet are already machined to fine tolerances, and (c) that is small (22 mm tall from skull to drive screw with screw at highest position), lightweight (0.39 g) and stable.
1, component 5). The length of this barrel will depend on the amount of travel required in the microdrive (typically we utilise a barrel length of 15 mm which provides for a travel of 2 mm). A notch is filed in one end of this tube to allow the electrode wires to escape from inside the drive. The fit of the nib end of the Bic™ ball point and its nylon support cylinder (i.e. the precursor of component 2, Fig. 1) is tested inside the aluminium tube. This should be an interference fit; loose enough so that it can be pushed through the tube, but not be so loose that it will fall under its own weight if the tube is held in the upright position. In our experience, the type of ballpoint pen (e.g. medium point, fine point) used can make a difference to this fit with each type having slight variations in the diameter of the nylon sleeve. If the nylon needs to be reduced slightly in diameter to allow for this level of fit, this is easily achieved by locating the item in an electric drill and holding fine abrasive paper against it as it rotates. If the nylon is too loose within the tubing, this can be overcome by gently squeezing the tubing (with the insert inside) until an interference fit is obtained. The nylon cylinder should now be cut in half (Fig. 1a, cut c 1) on the nib side of the flange and then shortened (Fig. 1a, cut c 2) to create component 2 of
2. Material and methods The basic principle of the design is simply that a rotational torque cannot be imparted to an object (a) if the two objects are not rigidly connected and if the only point of contact between the rotating and non-rotating objects is at the axis of rotation or (b) if the rotational force generated across the contact point between the two objects is insufficient to overcome the friction that prevents the driven object from rotating. The ‘Scribe’ microdrive described in this paper takes advantage of both of these principles. As can be seen in Fig. 1a, the movement of the driving screw is transferred to the electrode assembly via a conical device (that drives at or near the axis of rotation) that has a rolling ball mechanism at the tip (that minimises friction at the contact point). Although this conical/ball device would be expensive to machine from scratch, luckily it is readily available within the nib assembly of the ubiquitous ball-point pen.
3. Construction The metal ‘ball point’ section and the nylon cylinder that this ball point sits inside are extracted from the end of a standard Bic™ ball point pen. A section of aluminium tube (2.4 mm i.d., 3.15 mm o.d.) is cut to an appropriate length so as to create an outer barrel (Fig.
Fig. 1. The Scribe microdrive and its components. (a) The ballpoint and nylon sleeve after removal from the pen. Cut c 1 is required to separate (1), the pen nib (rear section), from (2), the pen nib (front section with ballpoint). Additional cuts (at approximately the location indicated by cut c2 and c3) may be required to shorten these two components. (b) Side view of the fully assembled microdrive: (1) pen nib (rear section); (2) pen nib (front section with ballpoint); (3) guide cannula; (4) electrode wires; (5) aluminium tubing; (6) hex-head drive screw.
D.K. Bilkey, G.M. Muir / Journal of Neuroscience Methods 92 (1999) 87–90
Fig. 1a. The remaining portion of the nylon sleeve can also be shortened (Fig. 1a, cut c3) to create component 1 of Fig. 1a. Component 1 is then glued into the end of the aluminium barrel without the notch. Note that the outside of the nylon and the inside of the aluminium tubing should first be scoured to assist the adhesion of the glue to these surfaces. A thread should then be tapped through the hole in the centre of this insert and the driving screw (e.g. 1/80 in. Hex Screw, 1/2 in. length, Small Parts Inc., Miami Lakes, FL) threaded into this hole. At this stage, the electrode assembly (Fig. 1, component 3) should be mounted into the open end of the nylon cylinder that holds the metal nib (Fig. 1, component 2). Our current electrode assembly is composed of a bundle of seven or eight 25 mm microwire electrodes threaded inside a 30 gauge (hypodermic needle) guide. The tail end of the electrodes are bent backwards to lie alongside the guide before the whole electrode assembly is glued inside the nylon tube. The guide is kept parallel to the main axis of the drive during the gluing process by supporting it in a simple jig. The device is then assembled by pushing the nylon tube and metal ball point into the aluminium barrel until the ball point touches the drive screw. The electrode wires are then routed out of the drive through the notch at the end and coated with liquid rubber (Color Guard™, Permatex Industrial, Newington, CT) to prevent these chafing against the inside edge of the notch. These electrodes can then be connected to a separate headplug assembly, either affixed to the microdrive itself or free-standing. The microdrive assembly should be mounted onto the surface of the skull so that the base of the aluminium barrel is against the bone and the tip of the guide cannula is several hundred microns above the dura. At this stage, the tip of the electrodes should be through a hole created in the dura and located immediately above the brain area of interest. The whole assembly can then be fixed in place by dental cement anchored to skull screws. A small quantity of petroleum jelly should be placed around the base of the drive to prevent dental cement flowing inside the barrel area. After the animal has recovered from the surgery, recordings can be conducted and the electrode can be advanced by small turns of the drive screw. Our experience is that 1/16 of a turn ( 20 mm) increments are possible.
4. Performance We have used the Scribe microdrive to record well isolated units in both the hippocampus and perirhinal cortex regions of the brain in freely-moving animals. Good quality recordings have been made in drives that have been implanted for up to 7 months and in some
89
Fig. 2. This figure provides an example of a stable hippocampal unit recording made with the scribe drive. The unit waveform (top) and corresponding ‘place field’ (firing rate plotted across the floor of the rectangular recording chamber; bottom) recorded on (a) day 1 and (b) day 4 of an experiment. Note that the location of the place field within the recording chamber is virtually unchanged across the 3-day delay indicating that the same cell was being recorded on day 1 and 4.
cases signal-to-noise ratios of up to 7:1 have been obtained. Stable recordings of individual units have been made for periods of up to 1 month (note that this time does not necessarily reflect the maximum time that a particular unit could be maintained, it merely reflects the duration of our recording protocol). An example of a recording from a hippocampal ‘place cell’ (Muller, 1996; Muir and Bilkey, 1999) is illustrated in Fig. 2, with recordings made from this unit during a baseline period (Fig. 2a) and then after a 3-day interval (Fig. 2b). The fact that the waveform is similar across recordings (Fig. 2a (top), Fig. 2b (top)) and that the cell’s ‘place field’ is unchanged across this period (Fig. 2a (bottom), Fig. 2b (bottom)) is an indication that the same cell was being recorded in both sessions. In summary, we believe that this new microdrive is an advance over previous designs based around a single screw, primarily because of its ease of manufacture and small size (Goldberg et al., 1993). These factors make it very suitable for multiple-site, multiple-drive applications. As it is described, however, it is lacking in a feature that some other, more complex designs (Deadwyler et al., 1979; Korshunov, 1995) exhibit. That is, it does not allow for electrode withdrawal, and thus the possibility of multiple penetrations. One possible means of achieving this goal, however, would involve mounting the electrode cannula off-centre inside the drive and clamping the whole assembly as described above inside
90
D.K. Bilkey, G.M. Muir / Journal of Neuroscience Methods 92 (1999) 87–90
a guide sleeve (a piece of tubing with an internal diameter equivalent to the outer diameter of the microdrive) that would be attached to the skull. At the end of a penetration the microdrive could be withdrawn from the guide tube, rotated so as to reposition the electrode and remounted into the guide. The potential for this type of modification will be investigated in future versions of the drive.
References Amos A, Armstrong DM, Harris R, Marple-Horvat DE. A lightweight hybrid microdrive for use with awake unrestrained animals. J Neurosci Methods 1989;28:219–24. Bland BH, Colom LV, Mani TE. An improved version of a direct-
.
drive, nonrotating manual microdrive. Brain Res Bull 1990;25:441 – 3. Deadwyler SA, Biela J, Rose G, West M, Lynch G. A microdrive for use with glass or metal microelectrodes in recording from freelymoving rats. Electroencephalogr Clin Neurophysiol 1979;47:752– 4. Goldberg E, Minerbo G, Smock T. An inexpensive microdrive for chronic single-unit recording. Brain Res Bull 1993;32:321–3. Korshunov VA. Miniature microdrive for extracellular recording of neuronal activity in freely moving animals. J Neurosci Methods 1995;57:77 – 80. Malpeli JG, Weyand TG, LaClair R. A new method of mounting and directing chronically implanted microdrives. J Neurosci Methods 1992;44:19 – 26. Muir GM, Bilkey DK. Instability in the place field location of hippocampal place cells following lesions of the perirhinal cortex. Soc Neurosci Abstr 1999; in press. Muller R. A quarter of a century of place cells. Neuron 1996;7:813–22.