Essential Role of the Hippocampal Formation in Rapid Learning of Higher-Order Sequential Associations

Evidence from studies of amnesia and functional imaging in humans suggest that the medial temporal lobe is involved in the learning of higher-order sequences during acquisition of serial reaction time (SRT) tasks. However, these studies have not clarified whether the hippocampal formation specifically is essential to this type of learning. Here, we developed a rodent model of the SRT task to examine the specific roles of the hippocampal formation in learning first- and second-order conditional sequences. Selective hippocampal formation lesions speeded performance and impaired accuracy on both first- and second-order sequences. Additionally, whereas controls distinguished the sequences based on their complexity alone, animals with hippocampal lesions initially differentiated sequences only by their length. Over multiple sessions, hippocampal rats gradually differentiated sequences by their complexity and not length, similar to control subjects. These findings indicate that the hippocampal formation itself plays an essential role in rapid acquisition of higher-order sequence representations. Extrahippocampal systems can also acquire complex sequential representations, albeit via a gradual learning mechanism.

[1]  L. Squire,et al.  Encapsulation of Implicit and Explicit Memory in Sequence Learning , 1998, Journal of Cognitive Neuroscience.

[2]  L. Squire,et al.  Perceptual learning, awareness, and the hippocampus , 2001, Hippocampus.

[3]  L. Squire,et al.  Parallel brain systems for learning with and without awareness. , 1994, Learning & memory.

[4]  W. Levy.  A computational approach to hippocampal function , 1989 .

[5]  C. Stern,et al.  An fMRI Study of the Role of the Medial Temporal Lobe in Implicit and Explicit Sequence Learning , 2003, Neuron.

[6]  Paul E. Gilbert,et al.  The role of the hippocampus in memory for the temporal order of a sequence of odors. , 2002, Behavioral neuroscience.

[7]  Daniel B. Willingham,et al.  Explicit and implicit remembering: When is learning preserved in amnesia? , 1989, Neuropsychologia.

[8]  M. Nissen,et al.  Implicit learning in patients with probable Alzheimer's disease , 1987, Neurology.

[9]  E. Rolls.  The hippocampus and memory , 1997 .

[10]  Howard Eichenbaum,et al.  The hippocampus and memory for "what," "where," and "when". , 2004, Learning & memory.

[11]  H. Eichenbaum,et al.  Critical role of the hippocampus in memory for sequences of events , 2002, Nature Neuroscience.

[12]  R. Kesner,et al.  A double dissociation between the rat hippocampus and medial caudoputamen in processing two forms of knowledge. , 2000, Behavioral neuroscience.

[13]  Raymond P. Kesner,et al.  Sequences assessed by declarative and procedural tests of memory in amnesic patients with hippocampal damage , 2004, Neuropsychologia.

[14]  H. Eichenbaum.  Hippocampus Cognitive Processes and Neural Representations that Underlie Declarative Memory , 2004, Neuron.

[15]  Tim Curran,et al.  Higher-Order Associative Learning in Amnesia: Evidence from the Serial Reaction Time Task , 1997, Journal of Cognitive Neuroscience.

[16]  E. Tulving,et al.  Episodic and semantic memory , 1972 .

[17]  M. Hasselmo,et al.  The hippocampus as an associator of discontiguous events , 1998, Trends in Neurosciences.

[18]  M. Nissen,et al.  Attentional requirements of learning: Evidence from performance measures , 1987, Cognitive Psychology.

[19]  L. Henderson,et al.  Serial reaction time learning and Parkinson's disease: Evidence for a procedural learning deficit , 1995, Neuropsychologia.

[20]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[21]  E. Maguire,et al.  The Human Hippocampus and Spatial and Episodic Memory , 2002, Neuron.

[22]  S. Keele,et al.  The cognitive and neural architecture of sequence representation. , 2003, Psychological review.

[23]  H. Eichenbaum,et al.  The Hippocampus and Disambiguation of Overlapping Sequences , 2002, The Journal of Neuroscience.

[24]  J. Gabrieli,et al.  Direct comparison of neural systems mediating conscious and unconscious skill learning. , 2002, Journal of neurophysiology.

[25]  J. Lisman.  Relating Hippocampal Circuitry to Function Recall of Memory Sequences by Reciprocal Dentate–CA3 Interactions , 1999, Neuron.

[26]  M. Nissen,et al.  Procedural learning is impaired in Huntington's disease: Evidence from the serial reaction time task , 1991, Neuropsychologia.

[27]  Albert K. Lee,et al.  Memory of Sequential Experience in the Hippocampus during Slow Wave Sleep , 2002, Neuron.