as mammals experience repetitions of sensory events, neurons in their sensory cortices gradually become tuned to specific features of those events. might similar processes explain the kinds of latent learning observed when individuals actively explore the world around them? one way that researchers have tried to answer this question is by measuring and manipulating brain activity in rodents performing spatial tasks. Initially, the emphasis was on discovering where mem-ories of mazes were stored in the cortex. Karl Lashley’s failed attempt to locate cortical engrams for maze learning in rats (described in Chapter 2) represents one of the earliest efforts. Later neurophysiological studies of rats navigating through mazes revealed that spatial learning actually depends much more on activity in the hippocampus than on cortical engrams.
the hippocampus is one of the most extensively studied brain regions in the field of learning and memory. In humans and other primates, it is a relatively small structure lying just beneath each temporal lobe (see figure 2.3 and figure 3.16a). In rodents, however, the hippocampus makes up a much larger proportion of the brain (figure 3.16b). many other vertebrates, includ-ing birds and reptiles, also possess a hippocampus. although the hippocampus in birds is proportionately smaller than in rodents (figure 3.16c), the size of a bird’s hippocampus is known to be important for spatial memory. specifically, bird species that store their food in many different locations for use in the winter have a hippocampus that is bigger than in related bird species that
Figure 3.16 The hippo-campus in several types of animals Cross sections showing the hippocampus in a monkey, rat, and bird.
Hippocampus within medial temporal lobes
(a) Monkey
Hippocampus (b) Rat
Hippocampus within medial temporal lobes
(a) Monkey
Hippocampus Hippocampus
(b) Rat
(c) Bird
Hippocampus within medial temporal lobes
(a) Monkey
Hippocampus Hippocampus
(b) Rat
(c) Bird
Gluck_3e_Ch03_Printer.indd 101 18/12/15 2:51 PM
do not need to keep track of hidden food (sherry & hoshooley, 2010).
generalizing across species, you might expect that given the size of their hippocampus, rats should be quite adept at spatial learning. this prediction is borne out by the success with which rats learned to traverse thousands of different mazes during the early history of psychological research.
Identifying Places
as a first step toward understanding the role of the hippocampus in spatial learning, english neuroscientist John o’Keefe implanted electrodes in rats’ hip-pocampal regions to record neuronal activity under various conditions (o’Keefe
& dostrovsky, 1971). when the rats were placed in an environment and allowed to explore freely, the investigators made a surprising discovery. some hippocam-pal neurons seemed to fire only when a rat wandered into particular locations, and other hippocampal neurons fired only when the rat was in other locations.
o’Keefe coined the term place cells to refer to neurons with such spatially tuned firing patterns. each of these neurons had a certain preferred location to which it responded with maximal activity, and this location was termed the place field for that neuron (analogous to the receptive fields of sensory cortical neurons described above). the activity of these cells was so reliable that a blindfolded researcher could tell when a rat entered a particular region of the maze just by hearing the corresponding place cell begin to fire. o’Keefe suggested that place cells might form the basis for spatial learning and navigation. In 2014, o’Keefe received a nobel prize for his contributions to this groundbreaking field of research.
how might place cells help with spatial navigation? If a certain neuron fires only when an individual is in a particular place, then that neuron might serve as an identifier for that place (much like road signs at street corners or mile mark-ers along the highway). when the neuron fires, the brain would then “know”
that the body is in a particular location. you could figure out where you are just by noting which place cell is firing. of course, if you were to begin life with enough place cells to code for every possible location you might ever visit, you would require an incredibly large number of place cells. such a method, in which cells are kept on reserve to encode locations that you haven’t yet visited, would be extremely wasteful. Instead, it would be smarter to create place cells as you need them. In other words, place fields should form during learning, as an animal explores its environment. this turns out to be the case.
an explanation of how place cells work must begin with a discussion of what defines a place. put another way, what exactly determines whether a place cell will respond? part of what leads a place cell to respond seems to be the animal’s inner sense of its location in space: a rat’s place cells often continue to respond in an orderly fashion even when the rat is running through a maze with the lights out. But place cell responses also depend heavily on visual inputs. for example, suppose a rat is allowed to explore a maze like the one shown in figure 3.17a.
this maze has three identical arms (labeled 1, 2, and 3 in the figure) differen-tiated by one salient visual cue: a card placed outside the maze between arms 2 and 3. after the initial exploration, various place cells in the rat’s hippocampus will have place fields corresponding to parts of this maze. one hippocampal neuron, for example, had the place field shown in figure 3.17b (darker areas indicate maximal firing; lighter areas, lesser firing). In other words, this place cell responded preferentially when the rat was in the southwest corner of the maze (as oriented in figure 3.17a), at the outer edge of arm 2, on the side near-est the card (Lenck-santini, save, & poucet, 2001).
now suppose the experimenter takes the rat out of the maze and rotates the maze and card 120 degrees clockwise. what do you think will happen when the rat is put back in the maze (figure 3.17c)? will the place cell continue to
place cell. A neuron that fires maximally when the organism enters a particular location within an environment.
brain SubStrateS
|
103fire when the rat is in the southwest corner of the maze? or will it fire when the rat is at the end of arm 2, even though that is now the north-most corner of the maze? the answer is shown in figure 3.17d: the place cell’s preferred location has rotated along with the maze. In this particular case, since the three arms all look, smell, and feel pretty similar, the rat probably used the visual cue as a land-mark. when the maze was rotated again, another 120 degrees clockwise, but the card was returned to its original place, to the west (figure 3.17e), then the place cell again fired in the southwest corner of the maze, even though this was now arm 3 (figure 3.17f). these findings illustrate the importance of visual land-marks (such as the card) in determining when a hippocampal place cell will fire.
In addition to landmarks, some place cells in rats seem to be sensitive to other variables, such as the speed or direction in which a rat is moving. thus, place cells respond like sensory cortical neurons with multimodal receptive fields.
some place cells have place fields that are stable for months: if the rat is returned to the maze in figure 3.17 after a long absence, the same place cell may still fire when the rat is in the same location as before. research also shows that when place fields are unstable, spatial navigation is disrupted. the stability of place fields and their selectivity in terms of particular visual scenes are consistent with the idea that place cells provide the basis for a “cognitive map” that rats use to navigate through the world. But how, exactly, do place cells become tuned to a particular place?
Card 3
2 1
3 (a)
None
Place cell firing rate
Low High
(c) (e)
(b) (d) (f)
2 1
2
1 3
1
3 2
2
1 3
1
3 2
Figure 3.17 Effects of a visual landmark on a rat’s place field Upper images show the rat’s environment: a three-armed maze and a visual cue (a card, location marked in dark purple). Lower images show how a representative place cell fires in this environment: dark areas are regions that evoke heavy firing; lighter areas, regions that evoke lesser firing. (a, b) When the maze is in its initial position, this place cell fires maximally when the rat is in arm 2. (c, d) When maze and cue card are rotated 120 degrees clockwise, the place field is determined by visual cues; maximal firing still occurs in arm 2. (e, f) If the maze is rotated another 120 degrees but the card is returned to its original location, the place cell fires when the rat is in the southwest corner, even though this is now arm 3. In other words, place cell firing seems to depend on the rat’s location relative to the visual landmark.
Data from Lenck-Santini et al., 2001.
one factor affecting the creation of place fields is experience. when rats repeatedly experience an environment, their place cells become increasingly tuned to locations within that environment (Lever, wills, Cacucci, Burgess, & o’Keefe, 2002). Imagine the size of the dark place field in figure 3.17 (b, d, and f) getting smaller and smaller, providing an increasingly precise and reliable report of where in the maze the rat is. this place-field shrinkage seems to correlate with rats’
spatial navigation abilities in a maze; experiments in which rats’ place-field shrink-age is disrupted (for example, by blocking inputs from the thalamus) show that the rats’ spatial learning abilities decline (Cooper & mizumori, 2001; mizumori, miya, & ward, 1994; rotenberg, abel, hawkins, Kandel, & muller, 2000).
place cells are not the only neurons in the temporal lobes tuned to spatial features. other neurons located in cortical regions surrounding the hippocampus show selectivity when an animal is headed in a particular direction (head direc-tion cells), or when animals cross through equal distances within an environment (called grid cells). although these neurons likely contribute to an individual’s abil-ity to learn about locations in ways that are similar to place cells, there is little evidence that the firing properties of head direction cells or grid cells are affected by repeated experiences with particular environments (gupta, Beer, Keller,
& hasselmo, 2014). this lack of evidence may mean that grid cells and head direction cells are less affected by learning experiences than are place cells, or that they are affected in different ways that haven’t yet been detected experimentally.
the findings presented above suggest that spatial learning that occurs during exploration is correlated with changes in the stability and selectivity of hippocampal neurons (rosenzweig, redish, mcnaughton, & Barnes, 2003).
this phenomenon may explain the latent learning by which tolman’s rats came to know the layout of a complex maze even without associating specific locations with food rewards. perhaps as the nonrewarded rats explored the maze, their place fields shrunk as much as (or more than) those of the rewarded rats, providing them with a precise representation of various locations within the maze that they could later take advantage of when the researchers initiated training with food.
Recognizing Familiar Objects
In order to use visual landmarks to navigate within a maze, rats must be able to recognize those landmarks. this suggests that as rats explore an environment, they not only learn how to navigate through that environment, but they also learn the properties of objects within and around the paths they are traveling.
recall that some of the earliest evidence of visual perceptual learning came from studies in which triangles and circles were mounted in the home cages of rats.
If neurons within the temporal lobes are sensitive to visual landmarks within a maze, might they also contribute to a rat’s ability to recognize novel objects and distinguish them from familiar landmarks?
several studies have examined this possibility in rats performing the novel object recognition task described earlier, as well as in monkeys performing shape recognition tasks. In early experiments, researchers lesioned the hippo-campus of rats after the rats repeatedly explored fixed configurations of objects.
rats with hippocampal damage showed impaired object recognition memory, exploring objects that they had experienced many times as if they had not seen them before. Later studies found, however, that such lesions disrupted object recognition in certain situations only (Langston & wood, 2010)—specifically, those in which memories of the position of the object and the context in which it was experienced were integrated. studies in cortical regions surrounding the hippocampus found neurons that fired differently when visual inputs were novel versus familiar (Xiang & Brown, 1998): those neurons responded less when familiar stimuli were presented.
CLiniCaL perSpeCtiVeS
|
105related findings are reported in humans. neuropsychological studies of patients with lesions to the hippocampus and surrounding cortical regions found impaired recognition of familiar objects (squire, wixted, & Clark, 2007).
neuroimaging studies, too, implicate regions in the temporal lobes in the detec-tion of familiarity and novelty, although there is debate about the specific roles that the hippocampus and cortical regions play. Intriguingly, electrical stimula-tion in cortical regions within the temporal lobes can produce feelings of deja vu in human patients, further implicating these regions in the detection of familiar-ity (Bartolomei et al., 2012).
overall, past findings suggest that neurons in the hippocampus and surrounding cortical regions contribute to exploratory learning in ways that go beyond simply constructing spatial maps or identifying familiar objects. these brain regions likely contribute to the encoding and retrieval of memories in numerous ways, some of which you will discover as you study further in this book. In addition, recent work suggests that other brain regions, including sensory cortices, may also play a pivotal role in mechanisms of novel object recognition and familiarity. for example, researchers studying mice have linked changes in the responses of neurons in primary visual cortex (V1) to both long-term habituation after repeated presentations of visual images and to the detec-tion of novel images (Cooke, Komorowski, Kaplan, gavornik, & Bear, 2015).
Local application of drugs that interfered with cortical plasticity in V1 blocked the behavioral changes associated with repeated exposures to images and also those produced by novel stimuli, showing that these behavioral changes were dependent on cortical plasticity in V1.
the new findings suggest that the processes underlying habituation, per-ceptual learning, and novel object recognition may be more closely linked than researchers previously thought. as you will see in the following section, discov-eries such as these not only can provide new insights into the processes underly-ing various forms of learnunderly-ing, but can also lead to new approaches to correctunderly-ing such processes when they are disrupted by brain disorders.
Interim Summary
■
■ In Aplysia, habituation is the result of synaptic depression in circuits that link sensory neurons to motor neurons. Long-term habituation involves physi-cal changes in the connections between these neurons.
■
■ sensitization in Aplysia reflects heterosynaptic increases in synaptic trans-mission caused by the activation of interneurons.
■
■ during perceptual learning, cortical neurons refine their responses to sen-sory inputs as discrimination abilities improve.
■
■ hippocampal place cells are neurons that become most active when an ani-mal is at a particular location. these neurons and other spatially sensitive cells in surrounding cortical regions may help animals identify and navigate through familiar environments.
■
■ neurons in the hippocampus and surrounding cortical regions also contrib-ute to the recognition of novel objects, giving rise to a sense of familiarity.
3.3 Clinical Perspectives
even though you are probably not consciously aware of it, habituation, sen-sitization, and perceptual learning influence every experience you have. from your ability to understand speech to your ability to find your way to school or
work, everything you perceive is influenced by the memories you’ve acquired through repeatedly experiencing similar stimuli. when neural circuits that process sensory information are damaged or when highly aversive events are experienced, the result can be a fundamental change in how stimuli are per-ceived, processed, and learned about, which in turn can affect one’s mental health and quality of life.