Pankaj Sah

Prof Sah's major interest has been in understanding the neural circuits that underpin learning and memory formation working on two regions that have well defined roles in learning: the hippocampus and amygdala. He have made major contributions to both these areas and pioneered whole-cell recordings in acute brain slices and provided the first biophysical characterisation of excitatory glutamatergic synapses in the mammalian brain (e.g. Hestrin et. al. 1990, J. Physiol. 422:203; Sah, et al. 1989 Science, 246:815). These synapses are involved in all activity in the central nervous system and our results are cited in major neuroscience textbooks (e.g. Kandel and Schwartz, Principles of Neural Science). Although the hippocampus plays a role in many forms of learning, linking hippocampal activity to specific behaviours has proven difficult. He therefore decided to study the amygdala, a region of the brain well known to play a key role in a very specific form of learning: fear conditioning. His laboratory has been a leader in studying the amygdala and provided the first characterisation of the properties of neurons in this structure (e.g. Faber et al., 2001 J. Neurophysiol. 85:714; Faber & Sah 2002, J. Neurosci. 22:1618). revealing a number of novel and unexpected properties of central synapses and changed thinking about the functional roles of different synapses. For example, it was thought that learning only engaged synaptic plasticity at excitatory synapses on pyramidal neurons. His group showed that in the amygdala a unique form of plasticity also occurs in interneurons (Mahanty & Sah 1998, Nature 394:683) and have recently shown that this plasticity is restricted to a single class of interneuron (Polepalli et al. 2010, J Neurosci. 30:14619). Much of his group's work in this area formed the basis of an influential review (Sah et al. 2003, Physiological Reviews 83: 803). In 2005, my laboratory also discovered that small conductance calcium-activated potassium channels, known to set the discharge properties of central neurons, are also present at excitatory synapses where their modulation plays a key role in setting the strength of synaptic connections and in synaptic plasticity (Faber et al. 2005, Nature Neurosci 8:635). Moreover, these channels are modulated by the hormone noradrenaline, explaining how memory formation may be affected by stressful stimuli (Faber et al. 2008, J Neurosci. 28:10803). Finally, interneurons in the adult brain were though to only be inhibitory. The Sah laboratory demonstrated that a particular type of interneuron in the amygdala is excitatory (Woodruff et al. 2006, J. Neurosci. 26:11881) overturning a long-standing dogma in the field. Interneurons in the amygdala have long been known to play an important role in amygdala-dependent learning. These effects were thought to result from the inhibitory actions of interneurons on the output neurons of the amygdala. His group's results are showing that these cells play a central and unexpected role in information processing and are redefining our understanding of the function that interneurons play in intrinsic circuits in the amygdala.